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Analysis of Serum Th1/Th2 Cytokine Levels in Patients with Acute Mumps

Infection

Article  in  Journal of global infectious diseases · February 2016

DOI: 10.4103/0974-777X.182129

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ORIGINAL ARTICLE

1 Analysis of Serum Th1/Th2 Cytokine Levels in Patients with Acute 1

2 2
3 Mumps Infection 3
4 4
5 Jeevan Malaiyan, Padmasani Venkat Ramanan1, Dinesh Subramaniam, Thangam Menon 5
6 6
7 Department of Microbiology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, 1Department 7
of Pediatrics, Sri Ramachandra Medical College and Research Institute, Porur, Chennai, Tamil Nadu, India
8 8
9 9
10 10
11 ABSTRACT 11
12 12
Background: The mumps virus is frequently the causative agent of parotitis. There has been no study on serum cytokine
13 13
levels of acute mumps parotitis except for a few which document cytokine levels in cerebrospinal fluid of mumps meningitis.
14 It is with this notion, our study aimed to find Th1/Th2 cytokine levels from patients with acute mumps parotitis. Materials and 14
15 Methods: Concentrations of mumps-specific IgM, mumps, measles, rubella-specific IgG antibody, and Th1/Th2 cytokines, 15
16 namely interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-10 were measured simultaneously in serum from 74 patients 16
17 (42 pediatric and 32 adult cases), 40 healthy subjects (20 pediatric and 20 adults) and in the supernatant of peripheral blood 17
mononuclear cells stimulated with mumps virus genotype C which served as the positive control. Statistical significance was
18 18
analyzed between each group by means of Mann–Whitney U-test, Kruskal–Wallis test, and Spearman’s rank correlation
19 coefficient test. Results: IgM positivity confirmed acute infection in all 74 patients and of these 67 were vaccinated cases; 19
20 however, very few of them (10/67) were positive for mumps IgG. We found that IFN-γ, IL-2, and IL-10 showed a statistically 20
21 significant increase in both pediatric and adult patients with acute mumps infection when compared to healthy controls and 21
22 values were comparable to the positive control. Conclusion: The Th1 cells play important roles during the acute phase of 22
mumps parotitis.
23 23
24 24
Key words: Acute mumps, IgM and IgG antibodies, measles, mumps, rubella vaccine, Th1 and Th2 cytokines
25 25
26 26
27 27
28 28
29 INTRODUCTION postpubertal males. Mumps infection still prevails in 29
30 India because mumps virus vaccine has not been made 30
31
32
33
M umps is acute, highly contagious, systemic,
communicable viral infection found throughout
the world, characterized by parotitis of one or both
mandatory for children.[5,6] It is generally believed that
pro-inflammatory interferon-γ (IFN-γ) responses prevail
31
32
33
at the sites of infection, while the systemic response is
34 salivary glands (90%), aseptic meningitis (−15%), transient anti-inflammatory interleukin-10 (IL-10). There have 34
35 deafness (−4%), and encephalitis (−0.1%). Other clinical been no reports on serum/plasma cytokines levels in 35
36 features include orchitis (20–38% in postpubertal males), 36
mumps infection except for a few studies documenting
37 oophoritis (0.5–7%), and respiratory symptoms (40–50%). 37
cerebrospinal fluid (CSF) cytokine levels in mumps
38 Transmission occurs through inhalation of respiratory 38
mediated meningitis in comparison with other viral
39 droplets or by direct person-to-person contact; reinfection 39
40 may occur after natural infection.[1-4] 40
Address for correspondence:
41 Dr. Thangam Menon, E-mail: thangam56@gmail.com 41
42 Mumps infection is not rare in childhood and adults, 42
43 but sometimes severe complications arise in the form This is an open access article distributed under the terms of the 43
44 of meningitis and deafness in children or orchitis in Creative Commons Attribution-NonCommercial-ShareAlike 3.0 44
License, which allows others to remix, tweak, and build upon the
45 work non-commercially, as long as the author is credited and the
45
46 Access this article online
new creations are licensed under the identical terms. 46
Quick Response Code:
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For reprints contact: reprints@medknow.com
48 www.jgid.org 48
49 How to cite this article: We will update details while making issue online*** 49
50 DOI:
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© 2016 Journal of Global Infectious Diseases | Published by Wolters Kluwer - Medknow 19
 Jeevan, et al.: Cytokine levels in patients with acute mumps infection

1 meningitis and a ferret in vivo model.[7-12] The aim of our Determination of antibody and cytokine concentrations 1
2 study was to determine reflection of specific mechanisms 2
3 of host response to mumps infection by analyzing the Serum samples were tested for mumps-specific IgM 3
4 serum cytokine levels of Th1 (IFN-γ and IL-2), Th2 (IL- antibody by ELISA (Labor Diagnostika Nord GmbH 4
5 4 and IL-10) in children and adults with acute mumps and Co., KG, Germany), and MMR-specific quantitative 5
6 infection. IgG ELISA (Techno Genetics, Italy) was done to quantify 6
7 MMR-induced specific IgG antibody in all participants, 7
8 in order to confirm that they had been vaccinated. 8
MATERIALS AND METHODS
9 IgG antibody titers were calculated from the sample 9
10 Patient sample collection absorbance and reference standard curve generated from 10
11 the reference sera provided with the kit. IgG antibody titers 11
12 For the selection of mumps cases, WHO guidelines were of >115 mU/ml for mumps, >115 mIU/ml for measles, 12
13 adopted.[3,13] An informed consent, proforma, and human and >15 IU/ml for rubella were defined as seropositivity. 13
14 ethical clearance for sample collection were obtained. Blood 14
15 Serum samples and culture supernatants were tested for 15
was collected from patients at the outpatient department of
16 Th1 cytokines and Th2 cytokines by standard ELISA 16
V. K. Nursing Home and Sri Ramachandra Medical College
17 as described before. [16] Cytokines evaluated in this 17
and Research Institute, Chennai, India. The sample was
18 study were the Th1 cytokines, IFN-γ (BD Pharmingen 18
collected 1-7 days after onset (average = 3 days). Following
19 Cat. No. 555142) and IL-2 (Cat. No. 555190), and 19
collection, samples were allowed to clot, then centrifuged
20 Th2 cytokines IL-10 (Cat. No.555157) and IL-4 (Cat. 20
at 1500 rpm for 5 min in order to remove cells, and serum
21 No.555194). Cytokine evaluation was done as per 21
was separated, divided into aliquots and immediately stored
22 manufacturer’s instructions. Briefly, all wells of 96 well- 22
at −86°C until use.
23 microtiter plates were manually coated with 100 µl of 23
24 capture antibody/well and kept at 4°C overnight. After 24
Controls
25 overnight incubation, the plates were washed with wash 25
26 The negative control groups consist of afebrile, noninfected buffer 3 times. Wells were blocked with 200 µl/well-assay 26
27 and nonmeasles, mumps, and rubella (MMR) vaccinated diluent and incubated at room temperature for 1 h. After 27
28 subjects (20 pediatric and 20 adults) aged from 5 years to washing, standards, test serum, and culture supernatants 28
29 20 years. Patients and control subjects having a history were added to appropriate wells. The plates were sealed 29
30 and incubated for 2 h at room temperature. The plates 30
of recent infections, receiving prolonged steroid therapy,
31 were washed again for 5 times, and 100 µl/well of 31
central nervous system disorders, convulsions or epilepsy,
32 working detector (detection antibody + SAv-horseradish 32
those who received blood, plasma, or immunoglobulin
33 peroxidase streptavidin) was added and incubated for 33
within the last 3 months, those diagnosed with malignancy
34 1 h, after which the plate was washed 7  times. Finally, 34
or immunodeficiency diseases were excluded from the
35 100 µl/well of 3′,5,5′-tetramethylbenzidine substrate 35
36 study. 36
was added; incubated in a dark room for 30 min, and the
37 reaction was stopped by adding 50 µl/well-stop solution. 37
For positive control, human blood was obtained from
38 The absorbance was then read using an ELISA reader at 38
healthy donors (Blood Bank, Voluntary Health Services,
39 450 nm wavelength. Concentration of each cytokine of 39
40 Chennai, India). Peripheral blood mononuclear cell 40
the sample was calculated based on the standard curve.
41 (PBMC) isolation was done by using Histopaque (Sigma 41
All assays were repeated thrice, and the results were
42 Cat No. 1077), and the procedure used was as directed 42
represented as the average (mean) of 3 experiments.[17]
43 by the manufacturer.[14,15] Isolated PBMCs were plated 43
44 at a concentration of 2 ×106 cells/ml/well in 24 well- Statistical analysis 44
45 tissue culture plates and infected with 50 µl of (5000 45
46 tissue culture infectious dose [TCID]50) mumps virus Values were reported as the median with range, and 46
47 genetype C (virus positive control) as described earlier.[4,16] differences in the results between two groups were 47
48 Cells were stimulated with 5 µg/ml of mitogen that is analyzed by means of student t-test and nonparametric 48
49 phytohemagglutinin ([PHA] - positive control [assay Mann–Whitney U-test. Difference between more than 49
50 control]). Plates were incubated in a CO2 incubator at 37°C two groups was analyzed by means of One-way ANOVA 50
51 for 72 h. After 72 h culture supernatants were collected, and nonparametric Kruskal–Wallis test. A P < 0.05 was 51
52 aliquoted, and immediately stored at −86°C until use. considered to be statistically significant. Correlations were 52
20 Journal of Global Infectious Diseases / Jan-Mar 2016 / Vol-8 / Issue-1
 Jeevan, et al.: Cytokine levels in patients with acute mumps infection

1 analyzed with use of Spearman’s rank correlation coefficient 0.9 pg/ml, and 1.95 pg/ml, respectively. The concentrations 1
2 test. For all the above analyses, a GraphPad Prism 6. below the detection limit were taken as 0 pg/ml. The 2
3 median and concentration range of the pediatric control 3
4 RESULTS subjects were 11.2 (9.6-17.61 pg/ml), 2.7 (1.26-6.15 pg/ml), 4
5 0 (0–3.01 pg/ml), and 2 (0-3.2 pg/ml), respectively and in 5
6 Patient demographic and antibody analysis adult control were 15.1 (9.74-23.6 pg/ml), 6 (1.98-8.91 pg/ml), 6
7 0.9 (0-3.24 pg/ml), and 2.2 (0-3.68 pg/ml), respectively. 7
8 A total of 74 mumps parotitis cases were collected over a Genotype C of mumps virus was isolated from our 8
9 period of 16 months (July 2011-November 2012). Of the previous study and quantified by TCID50.[18] The quantified 9
10 74 samples collected from various age groups, 42 (57%) virus was used for PBMC infection as virus control and 10
11 were from pediatrics with a median age of 6 years, and 32 the PHA used as assay positive control. The median 11
12 (43%) were from adults with a median age of 21 years. concentrations of virus control were 217.1 (210-223 pg/ml), 12
13 Of these, 54% were males and 46% were females. There 210.5 (192.6-206.4 pg/ml), 2 (1.94-2.12 pg/ml), and 194.2 13
14 was no significant difference in patients with regard to age (192.3-199.4 pg/ml), respectively [Table 2]. IFN-γ, IL-2, 14
15 and gender. Of the 74, 67 (91%) had been vaccinated, and and IL-10 showed a statistically significant increase in both 15
16 7 of them were nonvaccinated. Tests for mumps IgM in pediatric and adult acute mumps patients when compared 16
17 vaccinated cases indicated that an alarming 67/67 (100%) to healthy controls (pediatrics: P < 0.0001, P < 0.0001, 17
18 samples tested positive, whereas 57/67 (85%) samples P < 0.0001; and adults: P < 0.0001, P < 0.0001, P < 0.0001, 18
19 were negative for mumps IgG. These facts inevitably state respectively) and values were almost same and significant with 19
20 that MMR vaccine failed to offer protection in vaccinated virus control (P = 0.0075, P = 0.0302, P = 0.0003, respectively). 20
21 individuals against mumps infection. Around 67 (100%) IL-4 levels were slightly reduced when compared to controls 21
22 samples tested positive for rubella-specific IgG and P = 0.115, P = 0.0016, P = 0.0003 [Tables 2 and 3a, Figure 1]. 22
23 65 (97%) samples tested positive for measles-specific IgG, 23
24 suggesting that the mumps component in the MMR vaccine Correlation among immunological variables 24
25 had low efficacy. Of the 74 acute mumps cases, 7 of them 25
26 were nonvaccinated; mumps IgM was positive for these Table 3b shows the correlation among the pairs of measures 26
27 of IFN-γ, IL-2, IL-4, and IL-10 as represented by a 27
samples; however, they were negative for both mumps and
28 Spearman’s correlation matrix. The IFN-γ levels correlated 28
rubella IgG. Measles IgG was positive for these samples
29 with IL-10 and IL-2 in both pediatric and adult patients 29
because a separate measles vaccine is given at 9 months
30 (pediatric: r = 0·621, P < 0.00001; r = 0·523, P < 0.0004; 30
of age, prior to the MMR vaccine [Table 1]. The median
31 adult: r = 0·724, P < 0.000003; r = 0·026, P = 0.888, 31
value for mumps, measles, and rubella-specific IgG was
32 respectively) but did not correlate with IL-4 secretion. 32
422 mU/ml, 1009 mIU/ml, and 298 IU/ml, respectively.
33 33
34 34
Th1/Th2 cytokine profiles in acute mumps parotitis DISCUSSION
35 35
36 The lower detection limit of the IFN-γ, IL-2, IL-4, and IL-10 The immune system responds to viral infections by using a set 36
37 cytokines evaluated in this study was 2.35 pg/ml, 1.95 pg/ml, of cytokines that are beneficial to the host as they coordinate 37
38 38
39 39
40 Table 1: Details of patients with mumps infection and control subjects 40
41 Patients details Acute mumps — Pediatric cases Acute mumps — Adult cases Pediatric control Adult control 41
n 42 32 20 20
42 42
Age (median age) <12 years (6) 13-42 years (21) 5-12 years (8) 18-20 years (19)
43 Sex (male:female) 26:16 14:18 10:10 10:10
43
44 Onset of parotitis to sampling (average) 3 3 — — 44
45 (days) 45
Duration of fever (average) (days) 5 6 — —
46 MMR vaccination (%) 35/42 (83) 32 0 0
46
47 Number positive for mumps IgM antibody 42 32 — — 47
48 Number positive for mumps IgG antibody (%) 2/35 (6) 8/32 (27) 0 0 48
49 Number positive for measles IgG antibody 33/35 32/32 19 16 49
50 Number positive for rubella IgG antibody 35/35 25/32 0 0
50
Table shows the case distribution along with controls. A total of 74 patients with acute mumps were recruited in this study. Cases were divided into pediatrics (<12 years)
51 and adults (13–42 years). Of the 74 cases, all were positive for parotitis and mumps IgM. Of them, 67 (90%) patients had a clear MMR vaccine history while the others
51
52 7/74 (age of 20, 22, 23, 29, 36, 41, and 42) were nonvaccinated; MMR: Measles, mumps, and rubella 52
Journal of Global Infectious Diseases / Jan-Mar 2016 / Vol-8 / Issue-1 21
 Jeevan, et al.: Cytokine levels in patients with acute mumps infection

1 1
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40 40
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44 Figure 1: Serum concentrations of interferon-γ, interleukin-2, interleukin-4, and interleukin-10 in patients with mumps parotitis and controls. Data are 44
45 represented as medians with range. The interferon-γ, interleukin-2, and interleukin-10 levels of cytokine concentrations were higher in adult patients 45
46 when compared to pediatric patients. In adult and pediatric patients, the cytokine levels were comparable to virus control and higher when compared 46
to control subjects except interleukin-4. Interleukin-4 level was slightly reduced when compared to control (P = 0.115, P = 0.0016, P = 0.0003)
47 47
48 48
with host immune cells and eliminate viruses efficiently. The necrosis factor-β, whereas Th2 cells promote humoral immunity
49 49
50 Th cell response can be divided into Th1 or Th2 based on the and produce IL-4, IL-5, IL-6, IL-10, and IL-13.[19,20] T-cells that 50
51 pattern of cytokine secretion. Th1 cells promote cell-mediated produce cytokine pattern distinct from the well-defined Th-1/ 51
52 immune response and produce gamma IFN-γ, IL-2, and tumor Th-2 sets have been described as Th-0 and Th-17, etc.[19,21] 52
22 Journal of Global Infectious Diseases / Jan-Mar 2016 / Vol-8 / Issue-1
 Jeevan, et al.: Cytokine levels in patients with acute mumps infection

1 1
Table 2: Levels of cytokine concentrations (pg/mL) observed in this study
2 2
Groups IFN-γ IL-2
3 Range (pg/mL) Mean (pg/mL) Median (pg/mL) Range (pg/mL) Mean (pg/mL) Median (pg/mL)
3
4 A. Acute mumps - pediatric (42) 86.2-329.4 172.2 164.4 85.2-248.7 141.6 132.7 4
5 B. Acute mumps - adult (32) 110.1-329 209 200.4 89.8-325.5 143.1 138.6 5
6 C. Pediatric control (20) 9.6-17.61 11.6 11.2 1.26-6.15 3.2 2.7 6
D. Adult control (20) 9.74-23.6 15.5 15.1 1.98-8.91 5.5 6
7 7
E. Virus positive control 210-223 217.1 217.1 192.6-206.4 210.1 210.5
8 F. PHA positive control 325.6-246.1 240 240.2 392.6-401.5 397.1 397.2
8
9 Groups IL-4 IL-10 9
10 Range (pg/mL) Mean (pg/mL) Median (pg/mL) Range (pg/mL) Mean (pg/mL) Median (pg/mL) 10
11 A. Acute mumps - pediatric (42) 0-2.5 0.26 0 96.1-322.7 170.5 156.5 11
B. Acute mumps - adult (32) 0-3.2 0.22 0 27.4-365.1 229.7 254
12 12
C. Pediatric control (20) 0-3.01 0.91 0 0-3.2 1.3 2
13 D. Adult control (20) 0-3.24 1.2 0.9 0-3.68 1.8 2.234 13
14 E. Virus positive control 1.94-2.12 2.0 2.0 192.3-199.4 195.3 194.2 14
15 F. PHA positive control 420.6-435.6 427.6 426.8 229.1-236.4 232.3 231.6 15
16 IFN-γ: Interferon-γ; IL-2: Interleukin-2; IL-4: Interleukin-4; IL-10: Interleukin-10 16
17 17
18 Table 3a: Comparison of significant differences (P values) between the groups 18
19 Cytokines P
19
20 B versus A C versus A D versus B A versus B versus E A versus B versus F D versus C F versus E C versus D versus E C versus D versus F 20
21 IFN-γ 0.0036 <0.0001 <0.0001 0.0075 0.0042 <0.001 0.1000 <0.0001 <0.0001 21
22 IL-2 0.7884 <0.0001 <0.0001 0.0302 0.0135 0.0002 0.1000 <0.0001 <0.0001 22
IL-4 0.7952 0.0115 0.0016 0.0003 <0.0001 0.5039 0.1000 0.3804 0.0073
23 23
IL-10 <0.0001 <0.0001 <0.0001 0.0003 0.0003 0.2870 0.1000 0.0088 0.0088
24 24
IFN-γ: Interferon-γ; IL-2: Interleukin-2; IL-4: Interleukin-4; IL-10: Interleukin-10
25 25
26 lymphocytes (CTL) play an important role in CSF of mumps 26
27 Table 3b: Correlation between IFN-γ, IL-2, IL-4, 27
and IL-10 responses in study subjects as meningitis.[12,20] Taking these reports into consideration, a
28 28
represented by a Spearman’s correlation matrix higher level of IFN-γ in this study may indicate that IFN-γ
29 29
is mainly produced by CD8+CTL in serum of mumps
30 Variable Acute mumps — Pediatrics 30
P infection. On the other hand, levels of IL-2, a Th1 cytokine,
31 31
IFN-γ IL-2 IL-4 IL-10
elevated. This finding indicates the activation of CD4+ Th1
32 IFN-γ — <0.0004 0.510 <0.00001 32
cells. Therefore, it cannot be regarded that only CD8+CTL
33 IL-2 0.004 — 0.227 <0.00015 33
34 IL-4 0.5104 0.2274 — 0.426 produce IFN-γ in mumps infection because activated CD4+ 34
35 IL-10 1.25 <0.0002 0.426 — Th1 cells can also produce IFN-γ. With respect to the 35
36
Variable Acute mumps — Adults
P
cytokine levels in patient sera, we suggest that CD8+CTL 36
37 IFN-γ IL-2 IL-4 IL-10 and CD4+ Th1 cells play an important role in mumps during 37
38 IFN-γ — 0.888 0.965 <0.000003 the acute phase infection. An increased level of IL-10, which 38
39
IL-2 0.888 — 0.759 0.217468 is mainly produced by CD4+ Th2 cells, inhibits cytokine 39
IL-4 0.965 0.759 — 0.482792
40 production by CD4+ Th1 cells.[22,23] Therefore, we suggest 40
IL-10 2.7 0.217 0.483 —
41 IFN-γ: Interferon-γ; IL-2: Interleukin-2; IL-4: Interleukin-4; IL-10: Interleukin-10
that IL-10 is induced in response to higher production of 41
42 IFN-γ to modulate the balance of Th1 and Th2. The levels 42
43 In this study, we evaluated the ability of patients to respond of cytokine concentrations were higher in adult patients 43
44 to mumps virus by measuring cytokine levels. It is generally when compared to pediatric patients. In both adult and 44
45 believed that pro-inflammatory (IFN-γ), responses prevail pediatric patients, the cytokine levels were comparable to 45
46 virus control and higher when compared to control subjects. 46
at the sites of infection while the systemic response is
47 47
anti-inflammatory (IL-10). Our results showed that the There have been several reports on the immunological
48 48
49 simultaneous activation of pro and anti-inflammatory response to vaccine against the mumps virus. The mumps 49
50 immune responses in the serum may reflect the specific antigen-specific lymphoproliferative response to the vaccine 50
51 mechanisms of host response to mumps infection. The is comparable to that which occurs in naturally immune 51
52 previous studies demonstrated that CD8+cytotoxic T individuals and healthy control subjects. In response to 52
Journal of Global Infectious Diseases / Jan-Mar 2016 / Vol-8 / Issue-1 23
 Jeevan, et al.: Cytokine levels in patients with acute mumps infection

1 the mumps vaccine, serum IFN-γ, IL-10, and IL-12 are 7. Ichiyama T, Maeba S, Suenaga N, Saito K, Matsubara T, Furukawa S. Analysis 1
of cytokine levels in cerebrospinal fluid in mumps meningitis: Comparison
2 reported to be the central immunoregulatory cytokines.[24-27] with echovirus type 30 meningitis. Cytokine 2005;30:243-7.
2
3 The proinflammatory cytokine IFN-γ is a good indicator 8. Asano T, Ichiki K, Koizumi S, Kaizu K, Hatori T, Fujino O, et al. Enhanced 3
4 of antigen-specific cellular immunity while the anti- expression of cytokines/chemokines in cerebrospinal fluids in mumps 4
meningitis in children. Pediatr Int 2011;53:143-6.
5 inflammatory cytokines IL-10 and IL-13 may be important 5
9. Kaori K, Tatsuo F, Wakako I, Yuki I, Satomi T, Remi K, et al. Mumps-virus-
6 in maintaining sufficient humoral, or Th2 immune responses associated clinically mild encephalopathy with a reversible splenial lesion. 6
7 during antigen stimulation.[26] Low levels of IL-4 production Int J Clin Pediatr 2012;1:24-128. 7
8 are found in tissues affected by organ-specific autoimmune 10. Watanabe M, Suyama K, Hashimoto K, Sato M, Ohara S, Abe Y, et al. 8
Mumps virus-associated acute encephalopathy: Case report and review of
9 diseases, but this may simply reflect the relative dominance the literature. J Child Neurol 2013;28:243-5.
9
10 of inflammatory Th1 cells and few studies using animal 11. Parker L, Gilliland SM, Minor P, Schepelmann S. Assessment of the 10
11 model document increased production of IFN-γ and IL- ferret as an in vivo model for mumps virus infection. J Gen Virol 2013; 11
94(Pt 6):1200-5.
12 10 with strong absence of IL-4 and IL-5.[23,28] Our data 12
12. Martin R, Vallbracht A, Kreth HW. Interferon-gamma secretion by in vivo
13 also suggest same kind of results wherein IFN-γ and IL-10 activated cytotoxic T lymphocytes from the blood and cerebrospinal fluid 13
14 concentrations were significantly increased when compared during mumps meningitis. J Neuroimmunol 1991;33:191-8. 14
15 to control subjects with strong positive correlations and 13. Hindiyeh MY, Aboudy Y, Wohoush M, Shulman LM, Ram D, Levin T, et al. 15
Characterization of large mumps outbreak among vaccinated Palestinian
16 little-reduced level of IL-4 reflected by raised Th-1 cytokines. refugees. J Clin Microbiol 2009;47:560-5.
16
17 Furthermore, the stimulation of mumps virus-specific 14. Pandey R, Maurya R, Singh G, Sathiamoorthy B, Naik S. Immunosuppressive 17
18 memory cells in vaccinated individuals would have led to properties of flavonoids isolated from Boerhaavia diffusa Linn. Int 18
Immunopharmacol 2005;5:541-53.
19 the increased Th1 cytokine levels. In conclusion, the Th1 19
15. Mallone R, Mannering SI, Brooks-Worrell BM, Durinovic-Belló I, Cilio CM,
20 cells play important roles during the acute phase in the Wong FS, et al. Isolation and preservation of peripheral blood mononuclear 20
21 pathogenesis of mumps parotitis, and further studies are cells for analysis of islet antigen-reactive T cell responses: Position statement 21
22 of the T-Cell Workshop Committee of the Immunology of Diabetes Society. 22
needed to understand the immune response to mumps virus. Clin Exp Immunol 2011;163:33-49.
23 16. Nyland JF, Wang SB, Shirley DL, Santos EO, Ventura AM, de Souza JM,
23
24 Acknowledgment et al. Fetal and maternal immune responses to methylmercury exposure: A 24
25 cross-sectional study. Environ Res 2011;111:584-9. 25
We sincerely thank Dr. Srinivasan V, Dr. Chitra S, from V. K. 17. Janský L, Reymanová P, Kopecký J. Dynamics of cytokine production in
26 human peripheral blood mononuclear cells stimulated by LPS or infected
26
27 Nursing Home, Valasaravakkam, Chennai - 600 087, India, for 27
by Borrelia. Physiol Res 2003;52:593-8.
28 providing their help in obtaining serum samples. 18. Malayan J, Selvaraj B, Warrier A, Shanmugam S, Mathayan M, Menon T. 28
29 Anti-mumps virus activity by extracts of Mimosa pudica, a unique Indian 29
Financial support and sponsorship medicinal plant. Indian J Virol 2013;24:166-73.
30 19. Furuzawa-Carballeda J, Vargas-Rojas MI, Cabral AR. Autoimmune 30
31 Nil. inflammation from the Th17 perspective. Autoimmun Rev 2007;6:169-75. 31
32 20. Morishima T, Miyazu M, Ozaki T, Isomura S, Suzuki S. Local immunity in 32
mumps meningitis. Am J Dis Child 1980;134:1060-4.
33 Conflicts of interest 33
21. Thao D. Lippincott’s Illustrated Reviews: Immunology. Philadelphia:
34 Lippincott Williams & Wilkins; 2008. 34
35 There are no conflicts of interest. 22. Powrie F, Menon S, Coffman RL. Interleukin-4 and interleukin-10 synergize 35
36 to inhibit cell-mediated immunity in vivo. Eur J Immunol 1993;23:2223-9. 36
23. Flynn M, Mahon BP. Cell mediated and humoral immune responses to
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24 Journal of Global Infectious Diseases / Jan-Mar 2016 / Vol-8 / Issue-1

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