Psychoneuroimmunology and
health from a nursing perspective
Pauline Langley, Jenny Fonseca, Ron Iphofen
Abstract
Psychoneuroimmunology is the science that links psychological
processes and the immune system. It is important to nursing as it
offers underpinning theory to support good caring and empathetic
nursing. This article describes the science of psychoneuroimmunology
(PNI) and provides an overview of how interactions between
psychological states and physiological function take place and some
of the consequences for health status. It also reviews the relevance
of research to nursing and considers its potential to strengthen the
evidence base for therapeutic nursing and complementary therapies.
Key words: Stress n Immune response n Holistic care
P
sychoneuroimmunology (PNI) is an interdisciplinary
field of study of the interactions between psychological
processes and neurological, endocrine and immune
function, and their influence on health. Although
there had already been interest in psychosomatic interaction,
the current and sustained interdisciplinary research began in
the 1970s with work by Robert Ader who coined the term
PNI (Ader et al, 1991).
Developments in the pharmacological, biochemical
and physiological sciences together with technological
developments have contributed to the dominance of the
biomedical model in today’s orthodox medicine. This model
represents the body as a symptom-bearing organism, largely
distinct from the mind and separable into parts that can be
repaired on breakdown. It increasingly relies on technology
and highly sophisticated science with interventions
accordingly employing mainly surgery or drug therapy.
Orthodox medicine has had considerable success but like
many areas of modern life it is under regular scrutiny and has
come under attack in recent years for generating iatrogenic
illnesses, disempowering the patient and being overrated in
terms of efficacy (Pietroni, 1991). As a result of these criticisms
and dissatisfaction with the biomedical approach from both
the public and some members of the nursing profession and,
indeed, by many individual physicians, there has been an
increase in interest in and use of complementary therapies by
these groups (Pirotta et al, 2000). Such therapies have coexisted
alongside orthodox medicine for many decades, representing
Pauline Langley is Lecturer in Nursing, Jenny Fonseca is Lecturer in
Physiology and Ron Iphofen is Director of Postgraduate Studies, School
of Nursing, Midwifery and Health Studies, University of Wales, Bangor
Accepted for publication: September 2006
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another mode of care for a number of individuals. However,
what has not been so evident is a sound research base or
comprehensive and consensual scientific theory on which to
base these therapies.
This situation is slowly changing, as nurses, other health
professionals and complementary therapists become more
aware of the science of PNI. Research in this area has the
potential to validate aspects of care that nurses have intuitively
known to benefit their patients, as well as implement some
complementary therapies into nursing practice. Not all
complementary therapists would support their practice based
on the PNI research evidence, but what is common to all
complementary methods is the commitment of the patient
to take part in their own healing. It may be that we have yet
to discover some of the more subtle aspects of healing.
Research and psychoneuroimmunology
PNI began as a recognized field of study in the mid-1970s
when Ader demonstrated that a rat’s brain could influence
its immune system. In his classical conditioning experiment,
Ader provided rats with a series of paired stimuli consisting of
an oral saccharin solution stimulus and cyclophosphamide, a
drug known to produce a transitory decrease in the numbers
of T-lymphocytes and an associated immunosuppression.
Once the rats had recovered from the immunosuppression,
they were presented with the saccharin solution only.
Subsequent immune challenge and blood tests demonstrated
a decline in the T-lymphocyte count and a lack of antibody
response, indicating that the saccharine had become associated
with the immunosuppressive effect of cyclophosphamide,
and consequently, that immune function was capable of
modification by non-immune stimuli, i.e. that it was capable
of behavioural responses (Ader and Cohen, 1975).
Similar conditioned responses of the immune system have
been found in patients undergoing cytotoxic chemotherapy
for cancer. One common side-effect of chemotherapy is
a transitory immunosuppression. After several episodes of
treatment in the same hospital and room, patients returning to
that environment for a further episode of treatment were found
to be immunosuppressed on arrival (Bovbjerg et al, 1990). In
this case, purely psychological stimuli connected with the sight,
aroma or anticipation of the experience had become associated
with the treatment and induced the immunosuppressive effect
produced initially by the chemotherapy.
Physiology
Since the 1970s, there has been a significant increase in the
understanding of the physiological processes involved in
British Journal of Nursing, 2006, Vol 15, No 20

the mind-body interactions affecting health and illness. A
bi-directional communication system involving neural and
chemical signals acting between the brain or neuroendocrine
system and the immune system has been elucidated (Ader,
1996; Cohen and Herbert, 1996). During illness, the immune
system influences brain activity and behaviour through the
production of cytokines and their action on sensory neurones
or directly on the brain (Figure 1). Cytokines are used by the
immune system to coordinate its activities. However, some
cytokines also act as neurotransmitters, stimulating sensory
neurones in the viscera, particularly afferent vagal fibres, or
cross the blood-brain barrier, in each case affecting brain
or nervous system function (Blalock, 2005). Through these
channels they induce many of the generalized symptoms of
illness, including fever, increased sensitivity to pain, loss of
energy and interest in the usual daily activities of living, poor
appetite and sleep changes.These effects facilitate recovery and
are known as sickness behaviour (Hart, 1998; Kelley et al, 2003).
Cytokines also modify circulating hormone levels, particularly
cortisol which, at moderate levels, enhances immune activity
and promotes the release of nutrients from tissues to fuel the
changes in metabolic activity involved in healing and repair
processes (Looker and Gregson, 2003). This allows recovery to
begin despite poor food intake. It seems likely that cytokines
also induce the depression that may follow significant illness.
Acting in the reverse direction are two main pathways,
the hypothalamic-pituitary-adrenal (HPA) axis and the
autonomic nervous system, which allow the brain to
influence immune function (Figure 2), and through these
effects to influence the health status of the individual
(Blalock, 2005). The general physiological effects of these
systems are well understood, but what is perhaps less well
appreciated is their contribution to chronic and degenerative
illness. Both psychosocial and physical stressors tend to up-
regulate the HPA axis, producing an increase in circulating
cortisol levels. Additional significant stressors have a further
incremental effect. Also involved in the reaction to stressors
is the sympathetic nervous system, which innervates immune
organs and tissues such as the spleen and lymph nodes.
Chronic hyperactivation of the sympathetic nervous system
and HPA axis and their consequences for circulating cortisol
and catecholamine levels have the potential to dysregulate
immune function, producing complex and detrimental effects
on health (Padgett and Glaser, 2003). The particular nature of
Figure 1. Pathways of immune system-to-brain communication.
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holistic care
Figure 2. Pathways of brain-to-immune system communication.
these effects is determined to a large extent by factors such
as genetics, gender, personality, developmental effects, coping
styles and age (Kiecolt-Glaser et al, 2002, Lutgendorf and
Costanzo, 2003; Smith and Mackenzie, 2006).
The brain, therefore, has the capacity to fine-tune the
immune system, which can no longer be considered
autonomous (Black, 1994).
Stress and immunity
Over the past 20 years, PNI has developed into a legitimate
field of interdisciplinary research. Many of the studies in
this field focus on the effect of stress on immune function.
The term ‘stress’ is used in many different ways, usually to
indicate a physical, social or psychological stressor such as
pain, a distressing life event, or to indicate the effect of the
stressor on the physical or psychological state of the individual.
Independent of the type of stress, studies have repeatedly shown
it to have a detrimental effect on immune function increasing
the susceptibility to infection, and the likelihood of allergic or
hypersensitivity reactions (Rabin et al, 1989; Sapolsky, 1994).
Viral and bacterial challenges have been used to
demonstrate the increased susceptibility of both animals and
humans to infection when experiencing stress. In humans,
studies have generally been concerned with the effect of
psychological stress associated with experiencing such events
as academic examinations, divorce and caring for a spouse
with Alzheimer’s disease (Kiecolt-Glaser and Glaser, 1992).
Stressors for animals, which include such environmental
factors as overcrowding, high intensity sounds and cold
temperatures, increase morbidity from individual pathogens
(Black, 1994). Therefore, psychobiological stimuli, such as
pain and stress may activate both chemical and neural signals
resulting in suppressed or altered immune function which
increases the morbidity associated with individual pathogens.
It has also been demonstrated that methods used to reduce
the negative effects of stress, have the ability to enhance
immunity (Fawzy et al, 1993). However, Evans et al (1997)
suggest it is not as simple as this and individual measures
of the state of the immune system during stress may give
seemingly inconsistent pictures depending on the type of
stress, its duration and the timing of the measurements. They
suggest it is better to think of the immune system as striving
to maintain a state of delicate balance in which particular
activities of the system are constantly being ‘up-regulated’
or ‘down-regulated’ – terminology generally preferred by
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 PNI researchers as it more clearly implies a system where
fluctuation is the norm (Evans et al, 1997).
Homeostasis
Such fluctuation fits well with the concept of homeostasis,
i.e. the ability of the body to maintain internal stability,
despite environmental fluctuations. Adaptation according to
changing need can occur because the body is able to alter its
functions in a compensatory manner. Homeostasis is not a
static balance but a dynamic equilibrium in which continuous
change occurs and yet relatively uniform conditions prevail
(Rinomhota and Cooper, 1996). The term ‘homeostasis’ is
a concept of biological science which has been applied to
social systems theory, but the connection between health,
homeostasis and psychological functioning is rarely made in
orthodox medicine.
The main site of homeostatic regulation is the hypothalamus.
This region of the brain is closely linked to, and sometimes
regarded as part of, the limbic system (Rinomhota and
Cooper, 1996). Limbic connections extend to many areas of
the brain but particularly to the prefrontal cortex, which is
involved in cognitive processing and the evaluation of stimuli
with a potential emotional effect. As indicated by Hole
(1993) the limbic system recognizes situations that threaten
a person’s physical or psychological condition. Stimulation
activates centres in the hypothalamus responsible for initiating
the physiological responses. These include activation of the
sympathetic nervous system with effects typical of the ‘fight
or flight’ response, such as increased heart rate and blood
pressure, alterations in breathing and sweating and heightened
awareness of the external environment, and activation of
the HPA axis, which increases circulatory cortisol levels and
facilitates a sustained stress response (Hole, 1993).
Psychological influences on health
Psychological stressors have been linked to the development
and progression of cancerous tumours. In a case-controlled
study, Fawzy et al (1990) evaluated the effect of psychological
interventions to reduce stress in patients with stage I or II
malignant melanoma who were about to undergo surgical
excision of the tumour. They identified beneficial short-
term differences in the experimental group, which included
reduced psychological distress and significant immunological
changes. A six-year follow up of these patients showed a
trend toward greater recurrence and a statistically significant
higher mortality rate in the control patients than in the
intervention group (Fawzy et al, 1993).
In one landmark study of the effect of examination stress on
immune function, Glaser et al (1992) evaluated the response
to a series of three hepatitis B inoculations beginning on the
final day of a 3-day examination period. They found that the
students who seroconverted after the first inoculation were
significantly less stressed and anxious than the remainder,
and that those who responded most strongly to the final
inoculation had also reported greater social support during
the examination period. They concluded that the students
who were more stressed and more anxious might also be
slower to develop an antibody response to other pathogens
and could be at greater risk for more severe illness.
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Although there is considerable evidence to demonstrate the
relationships between psychological state and physical health,
PNI is still seen as a field ‘in development’ and some scientists
remain sceptical. Despite this and the need for more research
into aspects of health and illness, the value of this area of science
is gradually becoming accepted. Zeller et al (1996) suggest that
nurse scientists have been slow to use this framework for their
investigations but if suitably prepared, could lend a unique
perspective to PNI research by pursuing questions derived
from clinical care concerns, observations and experience.
Evidence-based practice
A major purpose of PNI research is to determine whether a
valid association exists between risk factors and the outcome
of immune status. Unfortunately, the methods used in this
type of evaluation are not easily available to nurse researchers,
who are often conducting research within severe resource
constraints. It is the medical practitioner who is said to have
clinical responsibility for patients. In the present-day health
service it is the doctor who will generally rely on information
collected from assessing parameters that identify physiological
status. They can request and will use laboratory investigations
to inform their practice, therefore it is more likely that they
will value and include such methods in their research protocol.
Conversely, nurses use broader parameters that consider the
physiological changes within a psychosocial context. It is
not normally part of nurses’ remit to request such things
as laboratory investigations, and this situation may result in
nurses avoiding biochemical or laboratory measurements in
their research, relying on more subjective measurements to
validate the effect of their nursing intervention. However,
studies to assess the value of holistic nursing interventions,
if designed with an integral PNI perspective, will allow
nurse researchers to evaluate what nurses claim to take into
account intuitively, that biological and behavioural processes
are tightly interwoven and both need to be considered when
providing patient care (Zeller et al, 1996).
The art and science of nursing
Nursing has been described as both an art and a science
and a complementary relationship exists between the two
(Greene, 1979). The nature of the relationship will vary
depending on how art and science are defined. Nurses
have often struggled to achieve a theoretical stance
between the insight of an artistic position and the rigour of
scientific evidence on which to base their practice. For the
purpose of this article science may be viewed as empirical
knowledge resulting from investigative efforts (Peplau,
1987; Smith, 1993).
The art in nursing refers to those things that can not be
accounted for by science.This has at times, led to a separation
of disciplines. While there is little definitive agreement as to
what constitutes the art of nursing, there is agreement that
it exists (Le Vasseur, 1999). Nursing has also been described
as a primarily intuitive practice (McCain, 1965) and nursing
interventions often as interpretive. Intuitive knowledge is
considered by many to be an essential component in the art
of nursing, involved in those things that nurses learn to do
conventionally in practice. It has been described by nurses in
British Journal of Nursing, 2006, Vol 15, No 20

many ways: the immediate knowing of something without
conscious reason – a creative discovery (Correnti, 1992).
Intuition is based on both knowledge and experience, and
the characteristics of an intuitive practitioner include an open
attitude towards people and an acceptance of non-traditional
treatment modalities (Young, 1987). Developments within
the science of PNI suggest that many of these intuitive caring
practices, such as holding a patient’s hand or rubbing their
back, that have developed without a theoretical base, may
now be shown to have a therapeutic value in physiological
fact (McCain et al, 2005).
Nurses have looked to alternative philosophies of science
and research methods that are compatible with investigations
of humanistic and holistic experiences to assess their value
in contributing to the wellbeing of patients. The conclusion,
based on current appreciation of psychoimmune interaction
would be that if the patient’s feelings of stress were relieved,
the perceived health gain would be achieved through
a corresponding beneficial effect on immune function.
If nursing is to be considered a practical science, the
complementary art and science of nursing would be properly
connected (Johnson, 1991).
Evidence indicates that relaxation and induced feelings
of contentment and happiness facilitate protective immune
function and enhance healing (Fawzy et al, 1993). Therefore,
if essential nursing care is delivered in a manner that enhances
these feelings, it may be considered that the art of nursing
has health benefits which can be supported by the science
of PNI. As health professionals are increasingly required to
justify their roles, this therapeutic benefit may encourage
nurses to retain ownership of the essential characteristics
of nursing care that can be seen to enhance the health and
wellbeing of their clients.
Conclusion
Since the 1970s there has been a growing body of information
and scientific research showing mind-body connections and
their influence on health and illness. It is this influence that has
encouraged some nurses to implement complementary therapies
into their practice. Many of these therapies are considered to be
holistic in their approach to care and involve mind-body
interaction. They are frequently used to assist an individual in
the management of a distressing condition but the pressure on
nurses working in acute clinical care areas may not allow them
the time to provide such therapies. From a nursing perspective
the science of PNI may be seen to be catching up with what
nurses have traditionally done – skilfully provide good nursing,
good caring, in an empathetic manner, knowing intuitively that
BJN
it will help their patients on their health journey.
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Key Points
n Psychoneuroimmunology is the study of psychological
processes and neurological, endocrine and immune
function, and their influence on health.
n Stress has been found to increase the susceptibility
of both animals and humans to infection.
n Relaxation and feelings of contentment and happiness
facilitate protective immune function and enhance
healing.
n Psychoneuroimmunology may offer the scientific
evidence to support health gains for the art of nursing.
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