Health Psychology Review Vol. 4, No.

1, March 2010, 4255

Social support and risk for cardiovascular disease and cancer: a qualitative review examining the role of inammatory processes
Lauren M. Penwell and Kevin T. Larkin*
Department of Psychology, West Virginia University, Morgantown, WV, USA (Received 25 March 2009; nal version received 18 October 2009) Social support has long been recognised as a protective factor against life stress and poor health. However, the mechanism through which it exerts its effects is unknown. As the role of inflammation in the development of diseases, such as cardiovascular disease and cancer, has gained significant attention over the last decade, it has been hypothesised that psychosocial factors affect disease progression by influencing the inflammatory process (Sher, 2000). Social support is one such factor that could influence the immune system response, leading to differing disease outcomes. A meditational model is proposed, in which social support affects the level of inflammation an individual experiences, producing differing health outcomes. A critical review of the literature linking social support and inflammation was conducted to help elucidate the relation between these two variables as possible causal factors of disease progression in patients with cardiovascular disease or cancer. Results of the studies were mixed, suggesting that social support and inflammation may be linked, though it is premature to claim that inflammation is the mechanism through which social support exerts salubrious effects on health. Keywords: social support; inammation; critical review; cardiovascular; IL-6; C-reactive protein; cancer; qualitative review

Chronic diseases top the list of the leading causes of death in the USA. Mortality statistics from 2005 implicated cardiovascular disease and cancer as the first and second leading causes of death, accounting for 26 and 22% of all deaths, respectively (Kung, Hoyert, Xu, & Murphy, 2008). Until prevention efforts are able to curtail the incidence of these chronic diseases, attention must be paid to the biological and psychosocial management of them. Although numerous behavioural risk factors (e.g., smoking, dietary factors, sedentary lifestyles) have been enumerated, considerable attention has been devoted to psychological stress as a risk factor for both cardiovascular disease and cancer (e.g., Andersen, 2002; Rozanksi, Blumenthal, & Kaplan, 1999). Effective coping with physical and emotional stress is an essential factor in positive health outcomes, and social support has been identified as a fundamental aspect of coping. In terms of its relations with health outcomes, poor social support has been linked with a more dismal prognosis and greater mortality in many diseases

*Corresponding author. Email: klarkin@wvu.edu

ISSN 1743-7199 print/ISSN 1743-7202 online # 2010 Taylor & Francis DOI: 10.1080/17437190903427546 http://www.informaworld.com

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(e.g., Berkman & Syme, 1979; Kroenke, Kubzansky, Schernhammer, Holmes, & Kawachi, 2006; Kumlin et al., 2001; Rozanski, Blumenthal, & Kaplan, 1999). Social support can be a nebulous concept to measure, with as many conceptualisations of it as there are measures for it. Cohen, Mermelstein, Kamarck, and Hoberman (1985) note that social support can be measured in a structural, quantitative sense (i.e., counting how many friends, relatives, activities, etc. an individual reports) or it can be measured qualitatively and functionally (i.e., regarding the quality of available confidants, emotional support, tangible support, etc.). Berkman, Glass, Brissette, and Seeman (2000) argue that social networks are fundamentally different from social support and social integration, though the terms are sometimes used indiscriminately. Social networks in and of themselves do not constitute social support, but they do provide the foundation for it to occur; they can be considered a quantitative measure of social support. The different facets of social support make it difficult to assess reliably for purposes of cross-study comparisons. Cohen and colleagues (1985) note that many measures of social support do not differentiate quantitative from qualitative aspects of support included within single instruments. To add complexity, not all social support is actually supportive; our relationships may produce both positive and negative effects. Despite the plethora of evidence linking social support to lowered risk for cardiovascular disease and cancer, the physiological mechanisms responsible for these associations have yet to be identified. Some have suggested that social support exerts its salubrious effect on health by reducing autonomic responses to stress (Uchino, 2006), and there is some empirical support for this hypothesis (e.g., Kamarck, Manuck, & Jennings, 1990; Turner-Cobb, Sephton, Koopman, BlakeMortimer, & Spiegel, 2000). However, as for the complex biochemical processes underlying the progression of cardiovascular disease and cancer, our knowledge is constantly evolving, and it is becoming increasingly clear that an inflammatory mechanism plays a significant role in these disease processes (Sher, 2000). Although, a thorough description of the immune system and the inflammatory process is beyond the scope of this paper, a basic understanding is integral to the critical review. Briefly, the immune response involves an attack upon foreign substances, generally bacteria or other infectious agents, to combat injury or infection, which is activated by the presence of these foreign substances. The immune system involves a myriad of different cells that respond to invasion of foreign substances or injury. A localised inflammatory response facilitates the healing process by making the vasculature more permeable, resulting in migration of immune cells into the wound or site of inflammation. Inflammation is driven largely by certain cytokines (known collectively as the proinflammatory cytokines) acting synergistically. The proinflammatory cytokines include tumour necrosis factor-alpha (TNF-a) and several interleukins, specifically IL-1-beta (IL-1b) and IL-6, which are produced by several types of white blood cells. Several intercellular adhesion molecules are also involved to help immune cells bind to targets to facilitate healing. However, the immune system (and inflammatory response) must remain in balance, as an overreaction can result in hypersensitivities or autoimmune disease, in which the immune system mistakes healthy cells for foreign substances and destroys them. Conversely, immune deficiencies can occur if the immune system is unable to respond to a foreign agent. An acute phase protein also involved in inflammation, C-reactive protein (CRP), has

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been implicated as a specific risk factor for cardiovascular disease (Abbas & Lichtman, 2001; Parham, 2009; Playfair & Chain, 2001). Several studies have shown that inflammation is associated with progression of illness and mortality in diseased individuals. Heikkila, Ebrahim, Rumley, Lowe, and Lawlor (2007) found that a doubling of serum IL-6 level was associated with an increased mortality hazard ratio among women with and without cancer, with women with cancer having slightly higher levels of IL-6 than women without cancer did. Higher concentrations of CRP were also associated with increased mortality both in women with and without cancer, indicating that these immune parameters were associated with risk of mortality, regardless of cancer status (Heikkila et al., 2007). In examining two large-scale studies of men and women, Pischon et al. (2008) found that IL-6, CRP, TNF-a and soluble intercellular adhesion molecule (sICAM1) were correlated with coronary heart disease (CHD) risk and metabolic syndrome, a cluster of physiological risk factors for CHD. Metabolic syndrome was a better predictor of CHD risk in women but was not significant in men when taking into consideration concentrations of CRP, suggesting that this particular inflammatory marker may have special significance as a risk factor for CHD. Likewise, Tang et al. (2007) found that sICAM-1 and monocyte chemoattractant protein (MCP-1), both inflammatory markers, were associated with greater atherosclerosis, but not significantly so when controlling for other risk factors for CHD. These studies suggest that inflammation is involved in the development of CHD, but perhaps the influence of other physiological or psychosocial factors will also need to be considered when considering CHD risk. The question pertinent to the current paper is whether social support influences the progression of cardiovascular disease and cancer by disrupting inflammatory processes. In brief, this constitutes what Baron and Kenny (1986) referred to as mediation, i.e., the relation between social support and disease endpoints is mediated by inflammatory processes. According to Baron and Kenny, mediation requires demonstrating that three relations exist: (a) social support is associated with disease endpoints; (b) the potential mediator (e.g., inflammation) is also associated with disease endpoints; and (c) social support is associated with the potential mediator. Mediation is then supported when all (or most) of the variance accounted for in the social support-disease link is explained by the potential mediator. Suffice it to say that no studies have been conducted that have directly examined the potential mediation of the social support-disease link by inflammation. However, as already noted, there is evidence that lack of social support is predictive of both cardiovascular disease and cancer outcomes (e.g., Kroenke et al., 2006; Kumlin et al., 2001; Rozanski et al., 1999), the first pre-requisite for demonstrating mediation. Secondly, inflammatory processes have been linked with both cardiovascular disease and cancer (e.g., Sher, 2000), satisfying the second pre-requisite for demonstrating mediation. The purpose of the current qualitative review is to examine evidence for the third pre-requisite for demonstrating mediation that a relation exists between social support and inflammation within the context of cardiovascular disease and cancer patients and the physiological processes involved in these diseases. If support for this component of the mediation model can be demonstrated, this would argue for additional empirical work examining all three elements of the meditational model. Given the relatively limited literature in this area of inquiry and the inconsistent methodologies employed, a quantitative review is not yet possible. Thus,

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the current review systematically examined each study in this literature qualitatively with the goal of determining whether evidence supports this path of the hypothesised mediation model. Although not conducted on cardiac or cancer patients, a study by Marsland, Sathanoori, Muldoon, and Manuck (2007) examined associations between several psychosocial risk factors, including social support, and a wide array of inflammatory markers in healthy adults. They found that better social support and greater size of social network were significantly associated with lower levels of IL-8, overall social support was associated with lower IL-6 and size of network was associated with lower TNF-a. When entered into a regression model controlling for potential confounding variables, only higher perceived social support was found to be predictive of lower IL-8 levels. Additionally, social network size was found to be correlated with several health behaviours and other psychosocial variables, but retained an independent predictive association with lower IL-8 (Marsland et al., 2007). Other studies on healthy samples have confirmed these findings (e.g., Friedman et al., 2005). While acute stress activates the immune system, chronic exposure to stress leads to immune system dysregulation. Decreasing the effects of stress upon the body via increased social support could be but one method of mitigating the risk for cardiovascular disease and cancer. Gidron and Ronson (2008) have proposed this same relation, including a prominent role of vagal stimulation in dampening the inflammatory dysregulation that contributes to tumourigenesis. The findings of these studies provide some initial support for this hypothesis, although it is important to examine the relation between social support and inflammation in persons with or at risk for cardiovascular disease or cancer, patients for whom inflammatory dysregulation may be the most problematic. Review criteria and organisation of the review Studies that examined the associations between social support and inflammatory markers were chosen from a search in CINAHL, Medline and PsycInfo via EbscoHost and PubMed. Studies were searched for using various combinations of the keywords inflammation, immune, interleukin, and social support. Searches were conducted separately for cardiovascular disease and cancer. Studies were excluded if they did not directly test the relation between social support and an inflammatory marker, if they used non-human populations or if they were review papers. Five studies focusing on the physiological processes underlying cardiovascular disease are presented first, as this disease has the largest impact on public health. The examination of cardiovascular disease studies include those conducted on clinical populations as well as those conducted on non-clinical populations at risk for CHD, to contribute to the understanding of the effects social support and inflammation may have on the pathogenesis of CHD. As studies dealing with social support and inflammation as related to cancer have focused on clinical populations, these studies were restricted to those using patient samples. Across disease areas, studies that were structurally similar or used the same variables were evaluated together. Within each disease domain, studies are presented in chronological order, to reflect the historical development of knowledge. In order to examine the literature critically within a coherent framework, special consideration was given to the integrity of each study design by examining: adequacy

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of the sample size; comprehensiveness in control for possible confounding variables; the reliability and validity of the social support measure used; the appropriateness of statistical analyses; the strength of the association found (if any); and any threats to internal or external validity in the experimental design. Specific study characteristics are displayed in Tables 1 and 2. The final column in each table notes whether a link between social support and inflammation was observed in each study. Review of the literature Cardiovascular disease Hemingway and colleagues (2003) noted the detrimental effects that inflammation had on endothelial integrity and sought to study the relation between social support, among other psychological variables and specific inflammatory markers related to endothelial dysfunction and consequently risk for CHD. The authors did not find a link between social support and any of the measures of vascular function or inflammation, though there was a negative association between civil service employment grade and CRP and IL-6 levels. In a sample of patients diagnosed with acute coronary syndrome, Gidron, Armon, Gilutz, and Huleihel (2003) measured the availability of emotional support in relation to several inflammatory variables. Emotional support and percent monocytes were inversely correlated, r 0(0.43, p B0.01, such that lower emotional support was associated with a greater aggregation of monocytes. No associations were found for the other inflammatory markers. Ford, Loucks, and Berkman (2006) conducted a survey to determine relations between inflammation and social activity across four domains: romantic relationships; familial and friendly relationships; religious practices; and volunteerism. Serum concentrations of CRP were measured, with levels of less than 3 mg/L being classified as low and concentrations greater than 3 mg/L being classified as high. As CRP is considered a risk factor for cardiovascular disease, the authors also questioned the participants about other potential risk factors for heart disease to use as covariates in study analyses. When adjusting for age, social integration was positively related with CRP concentrations in both men and women. Adjusting for age and race, social integration was related to CRP levels in men over the age of 60 and in women aged 2059. Finally, when controlling for all cardiovascular disease risk factors, the relation was only observed among men aged over 60. In age-adjusted analyses, 25% of the male participants with the lowest index of social integration had high serum CRP concentrations, while only 17% of the male participants with the most social integration had similar levels. Among women, 35% of the lowest socially integrated participants had high CRP levels, and 28% of the most socially integrated participants had high concentrations. Providing some consistency to the literature, significant associations were found between social support and IL-6 in men and women in a study by Loucks et al. (2006). When adjusting for all potential confounding variables, men in the lowest social bracket had a mean IL-6 concentration of 3.85 pg/ml and those in the highest social bracket had a mean concentration of 3.52 pg/ml. For women, the association was significant only when adjusting for age; the least socially integrated had a mean concentration of 3.98 pg/ml, and the most socially integrated had 3.47 pg/ml. Level

Table 1. Studies linking social support and inammation in cardiovascular disease. Study reference Hemingway et al. (2003) Measure of Measure of social support inflammation Close persons IL-6, CRP questionnaire Sample characteristics 283 civil servants; M age 054 yrs Exclusionary criteria Smoking Study limitations Covariates Link supported? No

Gidron, Armon, Gilutz, and Huleihel (2003) Ford, Loucks, and Berkman (2005)

Availability of Percent neutrophils, emotional monocytes, support lymphocytes SNI CRP

49 (80% M); M age058 yrs

Unverified diagnosis, age, lang Age

None reported Sample selection, control for confounding, social support instrument Lack of control, None reported social support instrument Insignificant Age, sex, race, edu, smoking, ETOH, PA, BMI, Chol, HTN, Health status Age, CHD risk, edu, depression

Yes (for percentage (%) of monocytes)

Health Psychology Review

14,818 (77% W, 47% M); M age044 yrs

Yes (particularly for older men)

Loucks et al. (2006) SNI

IL-6, CRP, sICAM-1, MCP-1

30763129 ( 48% M)

McDade, Hawkley, ISEL, UCLA CRP and Cacioppo Loneliness (2006) Scale

229 (55% F) M age059 yrs; 35% African-American, 35% Caucasian, 28% Hispanic

Not in seventh cycle of Framingham Offspring Study Non-ambulatory, lang

Insignificant

Yes (particularly for men)

CRP measured only once

Age, sex, race, edu, income

No

Note: SNI0Social Network Index; ISEL0Interpersonal Support Evaluation List; IL-60interleukin-6; CRP0C-reactive protein; sICAM0soluble intercellular adhesion molecule; MCP 0monocyte chemoattractant protein; W0white; F0female; M0male; Lang0not speaking predominant language of study population; ETOH0alcohol use; PA0physical activity; Chol0cholesterol; BMI0body mass index; HTN 0hypertension; Edu0education.

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Table 2. Studies linking social support and inammation in cancer. Study reference Lutgendorf, Anderson, Sorosky, Buller, and Lubaroff, (2000) Measure of social support COPE Measure of inflammation IL-6 Sample characteristics 21 women with gynecologic cancers'33 healthy controls, M age050 yrs Exclusionary criteria History of cancer, infectious disease, immunosuppressant meds within last 6 mos., psychiatric diagnosis History of cancer, ovarian germ cell cancer, tumour of another organ Metastatic cancer, lang Study limitations Covariates Link supported? Yes

Measurement of Smoking, education, age, social support, disease stage sample size

L.M. Penwell and K.T. Larkin

Lutgendorf et al. (2002)

Functional assessment of Cancer Therapy

VEGF

29 women with ovarian cancer; M age062 yrs

Sample size, control for confounding

Disease stage

Yes

Osborne et al. (2004)

Marucha, Crespin, Shelby, and Andersen (2005)

NKCA Duke-UNC Functional social support questionnaire TNF-a Katz Social Adjustment Scales, Dyadic Adjustment Scale Social Provisions Scale (SPS) IL-6

61 women with breast cancer; M age056 yrs 44 women with breast cancer (95% W); M age052 yrs 61 women with ovarian cancer (95% W); M age060 yrs

Control for confounding

Not specified

No

Costanzo et al. (2005)

Completion of cancer treatment less than 2 mos. before study, current disease Metastatic cancer, history of cancer, meds, immune disorder

Assessment methods

Disease stage

Yes

Assessment methods

Age, disease stage Yes

Table 2 (Continued) Study reference Lutgendorf et al. (2005) Measure of social support SPS Measure of inflammation NKCC Sample characteristics 65 women with ovarian cancer; M age056 yrs Exclusionary criteria Study limitations Control for confounding Covariates None reported Link supported? Yes

Von Ah, Kang, and Carpenter (2007)

Social Support Questionnaire -6 (satisfaction)

NKCA, IFN-g

Unconfirmed ovarian cancer, history of cancer, meds 54 women with Fewer than breast cancer; M seven days post-surgery, age 051 yrs; pregnant, 65% W, 26% previous Africanpsychiatric American diagnosis, immune disorder, meds

Social support instrument

No

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Note: VEGF is the abbreviation for vascular endothelial growth factor; NKC for natural killer cell; IFN for interferon; TNF for tumour necrosis factor; W for white; Meds for use of immunosuppressive medications.

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of social integration was significantly related to sICAM-1 levels only in men and only when adjusting for age. In this analysis, men reporting less social integration had an average of 263 ng/ml, and men reporting more social integration had a mean of 249 ng/ml. No significant associations were found between social support and CRP or MCP-1. The two studies by Loucks and colleagues support the hypothesis that social support is related to certain inflammatory risk factors for CHD more prominently among men than women. Both studies used large samples from ongoing epidemiological studies and the same measure of social support, although it only taps into structural aspects of social support (e.g., married vs. unmarried, frequency of activities). Dichotomising data on measures of social support for purposes of analysis also prohibited examination of the linear relation between these variables and excluded significant numbers of participants falling in the medial portions of the distribution. McDade, Hawkley, and Cacioppo (2006) also studied the effects of social support on CRP. This study is one of the few to examine loneliness in addition to perceived social support, which involved measuring appraisal, belonging and tangible aspects of social support. Satisfaction with social support was also assessed. In addition to social support and social isolation, the authors also surveyed participants about their levels of depression and stress. Neither social support nor loneliness was associated with CRP levels, nor did they serve as moderators in the associations between the other psychosocial variables and CRP concentrations (McDade et al., 2006).Although failing to support an association between social support and inflammation, this study had several strengths. Foremost, the sample included a greater diversity of participants than previous work, with roughly the same number of African-Americans as Caucasians and only slightly fewer Hispanics. The sample also included participants with diagnosed CHD that introduced several possible confounding variables, which unfortunately were not all used as covariates in study analyses. Participants with unusually high CRP concentrations were excluded from analyses, as per CDC recommendations. Some participant attrition was observed, but this was handled statistically by analysing characteristics of those participants who did not provide follow-up data. Cancer The vascular endothelium plays an important role in immune system functioning and in the promotion of tumour growth. Endothelial cells can be recruited as cancer cells and then enlarge through a process called angiogenesis, whereby new blood vessels are formed around tumours, feeding their growth. This process may be fuelled by a cytokine known as vascular endothelial growth factor (VEGF). There is preliminary evidence that social support is associated with dampened VEGF activity (Lutgendorf et al., 2002). Participants with less close ties to friends had higher levels of VEGF and participants with closer ties had lower levels of VEGF. Support from family was also predictive of lower VEGF levels. When dichotomised into high and low-VEGF group, participants with lower VEGF levels reported better social wellbeing than did participants in higher VEGF levels. Much of the research in the cancer literature has been conducted on women with suspected or confirmed ovarian or breast cancer. Within the breast cancer literature, Osborne and colleagues (2004) attempted to correlate social support and immune

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function. The instrument used measures perceptions of affective and confidant support. Although a small negative correlation was found between lymphocytes and confidant support, there were no associations between social support and other immune parameters or cortisol, and social support was not predictive of cancer survival. Marucha, Crespin, Shelby, and Andersen (2005) examined how frequency of social activities and satisfaction with a partner predicted levels of TNF-a, using an instrument that combined structural and functional aspects of social support. As frequency of social activities and partner satisfaction ratings changed during treatment, the residual change scores were used to predict TNF-a at 12-month follow-up. In conducting a series of regression analyses, they found that adding social activity to the regression model explained an additional 9.4% of the variance in TNF-a levels. Including partner satisfaction, in addition to frequency of activities, explained an additional 17.2% of the variance. Among the social variables, only partner satisfaction stood alone as a unique predictor of TNF-a. Costanzo and colleagues (2005) surveyed women with advanced-stage ovarian cancer about their satisfaction with their social relationships, specifically with regard to how well the relationships met certain needs. Women with poorer social attachment, defined by lower levels of satisfaction, had between 1.7 and 2.5 times more IL-6 than did women with better social attachment. This is notable because higher levels of IL-6 have been shown to contribute to the metastasis of tumours in ovarian cancer patients. Social attachment was the only subscale of the social support measure shown to have an association; guidance, reliable alliance, reassurance of worth, social integration and opportunity to provide nurturance all failed to predict IL-6 levels. Lutgendorf, Anderson, Sorosky, Buller, and Lubaroff (2000) reported similar results; additionally, patients utilising greater instrumental social support had less advanced disease and less functional disability at one-year follow-up. Because patients rely on an active immune responses to help combat tumour growth, some studies have examined measures of natural killer cell cytotoxicity (NKCC) and social support. For example, Lutgendorf et al. (2005) found that participants in their study reporting more distress had lower levels of NKCC and those reporting better perceived social support had higher levels of NKCC. Von Ah, Kang, and Carpenter (2007) also demonstrated that higher levels of stress were inversely related to Natural killer cell activity (NKCA) and IFN-g levels, though social support was not. Satisfaction with social support also did not moderate the association between stress and inflammation; optimism, in contrast, was shown to moderate the effects of stress on NKCA. Summary critique and conclusions The 12 studies that have examined the association between social support and inflammatory parameters and reviewed in this paper typically have been welldesigned, with specific research questions and coherent theories in mind. Analytic strategies were appropriate, and many threats to internal and external validity were minimised. In most studies using clinical patients, sample sizes were limited, which likely influences power to detect effects; interestingly, no studies reported how the sample size was determined and whether appropriate power analyses were

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conducted. Additionally, the cancer literature is somewhat narrow, focusing primarily on Caucasian women with breast cancers or ovarian cancers, thereby limiting generalisation to patients with other types of cancer. Among this literature, there is a critical lack of prospective studies. In order for there to be convincing evidence for an association between social support, inflammation and eventual disease outcomes, individuals should be recruited at the time of diagnosis and followed throughout disease progression, monitoring social support regularly. Mechanisms of action could also be proposed and tested, as prospective data collections represent the only viable method of testing whether social support affects disease progression by influencing the immune system. The causal pathway of interest cannot be confirmed using the correlational research studies examined in this paper, though findings from these cross-sectional studies represent a promising start. Studies of this nature would benefit by linking measurement of social support with our current conceptual understanding of social support. Measures of social support used in studies to date appear to be selected haphazardly, with no rationale regarding which aspect of social support is being measured and why one particular aspect of social support might be more important than another. Rarely are the negative aspects of social support considered, nor is the distinction made between perceived and objective support. Although structured and validated instruments have been used, some researchers opt to assess social support using self-generated rating forms, greatly reducing the credibility of the measurement and the validity of the study. Rationales for and psychometric properties of the instruments used are often absent, shedding some doubt on their appropriateness. Looking to the pioneers in the field could help to inform decisions regarding appropriate measures of social support. For example, Cohen developed the Interpersonal Support Evaluation List, Berkman and colleagues have utilised the Social Network Index and a group of researchers at the University of Miami have consistently used the Social Provisions Scale. These measures have proven useful in healthcare settings. In addition to an examination of the benefits of social support, the negative effects of social relationships should also be considered. Negative or stressful interpersonal relationships could influence whether inflammation functions to mediate the social support disease relation. Given the limitations of studies that comprise this literature, just what can be concluded about the relation of social support and inflammation with respect to these diseases? Weighting studies based upon their methodological limitations, results are mixed. Several well-designed studies showed that high levels of social support were predictive of lower levels of inflammation, or that lower levels of support were predictive of higher levels of these proteins, possibly to an unhealthy degree (Costanzo et al., 2005; Ford et al., 2006; Loucks et al., 2006; Lutgendorf et al., 2000, 2002; Marsland et al., 2007; Marucha et al., 2005), and some found associations between social support and other physiological measures related to immune function more generally (Lutgendorf et al., 2005). As a group, these studies tentatively support the hypothesis that social support and inflammation are related, albeit without specifying the exact physiological mechanism through which they are linked. Other well-designed studies, however, failed to reveal the hypothesised relation (Hemingway et al., 2003; McDade et al., 2006; Osborne et al., 2004; Von Ah et al., 2007). Replication of these studies by addressing some of the limitations noted

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above could help define more clearly the boundaries of the association between social support and inflammation. Among the studies that found significant associations, the strongest support for a link with social support was with the interleukins (Costanzo et al., 2005; Loucks et al., 2006; Lutgendorf et al., 2000; Marsland et al., 2007). However, this is not to say that the research involving other inflammatory markers should be discontinued. Rather, because the results have been mixed, additional well-controlled studies should be conducted to examine the effects of markers like CRP, given its presumed importance in CHD. As such, progress in the social support and inflammation literature could continue by incorporating some of the following directions in future research: (1) Expanding cancer research to examine other forms of cancer and more diverse samples (i.e., males and other participants with different demographic characteristics). (2) Conducting longitudinal studies that test specific pathways to help determine whether the correlational findings that have been observed correspond to any causal relations among variables. (3) Examining the full social supportinflammationdisease meditational model on samples of patients diagnosed and being treated for cardiovascular disease and cancer. (4) Providing convincing rationales for obtaining both quantitative and qualitative measures of social support. In conclusion, there is limited evidence to support the proposition that positive aspects of social support are associated with reduced inflammation. At this time, the lack of a single, consistently used social support instrument and the wide variety of inflammatory markers being studied make it difficult to clearly identify any consistent relations, which also prevent meaningful quantitative reviews of this literature. Other important variables involved in the relation between social support and cardiovascular and cancer disease processes need to be identified and the exact role that social support plays in mediating this relation needs to be more carefully studied. More studies that improve and expand upon the existing literature will need to be conducted to help state more conclusively if social support exerts its influence upon disease endpoints by reducing or promoting inflammation. Regardless of the state of the literature regarding social supports exact role in reducing risk for disease outcomes, clinicians can confidently encourage their patients to develop positive social relationships in order to better their overall health and quality of life.

Acknowledgements
We would like to thank John B. Barnett, PhD, of the WVU School of Medicine for his consultation on immunology questions.

References
Abbas, A.K., & Lichtman, A.H. (2001). Basic immunology: Functions and disorders of the immune system. Philadelphia, PA: W.B. Saunders Company. Andersen, B.L. (2002). Biobehavioral outcomes following psychological interventions for cancer patients. Journal of Consulting and Clinical Psychology, 70, 590610.

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Baron, R.M., & Kenny, D.A. (1986). The moderator-mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. Journal of Personality and Social Psychology, 51, 11731182. Berkman, L.F., Glass, T., Brissette, I., & Seeman, T.E. (2000). From social integration to health: Durkheim in the new millennium. Social Science and Medicine, 51, 843857. Berkman, L.F., & Syme, S.L. (1979). Social networks, host resistance, and mortality: A nineyear follow-up study of Alameda County residents. American Journal of Epidemiology, 109, 186204. Cohen, S., Mermelstein, R., Kamarck, T., & Hoberman, H.M. (1985). Measuring the functional components of social support. In I.G. Sarason & B.R. Sarason (Eds.), Social support: Theory, research and applications (pp. 7394). Dordrecht: Martinus Nijhoff. Costanzo, E.S., Lutgendorf, S.K., Sood, A.K., Anderson, B., Sorosky, J., & Lubaroff, D.M. (2005). Psychosocial factors and interleukin-6 among women with advanced ovarian cancer. Cancer, 104, 305313. Ford, E.S., Loucks, E.B., & Berkman, L.F. (2005). Social integration and concentrations of Creactive protein among US adults. Annals of Epidemiology, 16, 7884. Friedman, E.M., Hayney, M.S., Love, G.D., Urry, H.L., Rosenkranz, M.A., & Davidson, R.J. et al. (2005). Social relationships, sleep quality, and interleukin-6 in aging women. PNAS, 102, 1875718762. Gidron, Y., Armon, T., Gilutz, H., & Huleihel, M. (2003). Psychological factors correlate meaningfully with percent-monocytes among acute coronary syndrome patients. Brain, Behavior, and Immunity, 17, 310315. Gidron, Y., & Ronson, A. (2008). Psychosocial factors, biological mediators, and cancer prognosis: A new look at an old story. Current Opinion in Oncology, 20, 386392. Heikkila, K., Ebrahim, S., Rumley, A., Lowe, G., & Lawlor, D.A. (2007). Associations of circulating c-reactive protein and interleukin-6 with survival in women with and without cancer: Findings from the British Womens Heart and Health Study. Cancer Epidemiology, Biomarkers and Prevention, 16, 11551159. Hemingway, H., Shipley, M., Mullen, M.J., Kumari, M., Brunner, E., Taylor, M., et al. (2003). Social and psychosocial inuences on inammatory markers and vascular function in civil servants (the Whitehall II study). The American Journal of Cardiology, 92, 984987. Kamarck, T.W., Manuck, S.B., & Jennings, J.R. (1990). Social support reduces cardiovascular reactivity to psychological challenge: A laboratory model. Psychosomatic Medicine, 52, 4258. Kroenke, C.E., Kubzansky, L.D., Schernhammer, E.S., Holmes, M.D., & Kawachi, I. (2006). Social networks, social support, and survival after breast cancer diagnosis. Journal of Clinical Oncology, 24, 11051111. Kumlin, L., Latscha, G., Orth-Gomer, K., Dimberg, L., Lanoiselee, C., Simon, A., et al. (2001). Marital status and cardiovascular risk in French and Swedish automotive industry workers: Cross-sectional results from the Renault-Volvo Coeur study. Journal of Internal Medicine, 249, 315323. Kung, H.C., Hoyert, D.L., Xu, J.Q., & Murphy, S.L. (2008). Deaths: Final data for 2005. National Vital Statistics Reports, 56, 1124. Loucks, E.B., Sullivan, L.M., DAgostino, R.B., Larson, M.G., Berkman, L.F., & Benjamin, E.J. (2006). Social networks and inammatory markers in the Framingham Heart Study. Journal of Biosocial Science, 38, 835842. Lutgendorf, S.K., Anderson, B., Sorosky, J.I., Buller, R.E., & Lubaroff, D.M. (2000). Interleukin-6 and use of social support in gynecologic cancer patients. International Journal of Behavioral Medicine, 7, 127142. Lutgendorf, S.K., Johnsen, E.L., Cooper, B., Anderson, B., Sorosky, J.I., Buller, R.E., et al. (2002). Vascular endothelial growth factor and social support in patients with ovarian carcinoma. Cancer, 95, 808815. Lutgendorf, S.K., Sood, A.K., Anderson, B., McGinn, S., Maiseri, H., Dao, M., et al. (2005). Social support, psychological distress, and natural killer cell activity in ovarian cancer. Journal of Clinical Oncology, 23, 71057113.

Health Psychology Review

55

Marsland, A.L., Sathanoori, R., Muldoon, M.F., & Manuck, S.B. (2007). Stimulated production of interleukin-8 covaries with psychosocial risk factors for inammatory disease among middle-aged community volunteers. Brain, Behavior, and Immunity, 21, 218228. Marucha, P.T., Crespin, T.R., Shelby, R.A., & Andersen, B.L. (2005). TNF-a levels in cancer patients relate to social variables. Brain, Behavior, and Immunity, 19, 521525. McDade, T.W., Hawkley, L.C., & Cacioppo, J.T. (2006). Psychosocial and behavioral predictors of inammation in middle-aged and older adults: The Chicago health, aging, and social relations study. Psychosomatic Medicine, 68, 376381. Osborne, R.H., Sali, A., Aaronson, N.K., Elsworth, G.R., Mdzewski, B., & Sinclair, A.J. (2004). Immune function and adjustment style: Do they predict survival in breast cancer? Psycho-Oncology, 13, 199210. Parham, P. (2009). The immune system (3rd ed.). London: Garland Science. Pischon, T., Hu, F.B., Rexrode, K.M., Girman, C.J., Manson, J.E., & Rimm, E.B. (2008). Inammation, the metabolic syndrome, and risk of coronary heart disease in men and women. Atherosclerosis, 197, 392399. Playfair, G.H., & Chain, B.M. (2001). Immunology at a glance (7th ed.). London: Blackwell Science. Rozanski, A., Blumenthal, J.A., & Kaplan, J. (1999). Impact of psychological factors on the pathogenesis of cardiovascular disease and the implications for therapy. Circulation, 99, 21922217. Sher, L. (2000). The immune system and infection may be involved in the effects of psychological factors on the cardiovascular system. Australian and New Zealand Journal of Psychiatry, 34, 342. Tang, W., Pankow, J.S., Carr, J.J., Tracy, R.P., Bielinski, S.J., North, K.E., et al. (2007). Association of sICAM-1 and MCP-1 with coronary artery calcication in families enriched with coronary heart disease or hypertension: The NHLBI Family Heart Study. BMC Cardiovascular Disorders, 7, 111. Turner-Cobb, J.M., Sephton, S.E., Koopman, C., Blake-Mortimer, J., & Spiegel, D. (2000). Social support and salivary cortisol in women with metastatic breast cancer. Psychosomatic Medicine, 62, 337345. Uchino, B.N. (2006). Social support and health: A review of physiological processes potentially underlying links to disease outcomes. Journal of Behavioral Medicine, 29, 377387. Von Ah, D., Kang, D.H., & Carpenter, J.S. (2007). Stress, optimism, and social support: Impact on immune responses in breast cancer. Research in Nursing & Health, 30, 7283.

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