- Email: [email protected]
31. Therapeutic morphine prolongs neuropathic pain in rats: A role for TLR4 and inflammasome signaling in the lumbar spinal cord
Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52
In previous experiments, we have shown that spaceflight can alter leukocyte and lymphocyte population distributions and mitogen-induced cytokine expression. We hypothesize that these changes are a result of flight-induced physiological and psychological stress. On July 8, 2011, age- and weight-matched, female C57BL/6J mice were placed into Animal Enclosure Modules (AEMs) and flown on the Space Shuttle Atlantis (STS-135) for 13 days (N = 6–7). Ground controls were housed at the Space Life Science Laboratory (SLSL) at Kennedy Space Center (KSC). Ground AEM control mice were placed into the same hardware used in flight and environmental parameters such as temperature and CO2 levels were matched as closely as possible based on 48 h delayed telemetry data (N = 12–13). Vivarium control mice were housed in regular shoebox cages (N = 4). Mice were euthanized and dissected within 3–5 h of landing. Adrenals were removed, snap frozen in liquid N2, and shipped on ice back to Loma Linda University via overnight courier for analysis. Although corticosterone levels were slightly elevated in spaceflight mice, with a corresponding decrease in phosphorylated adrenocorticotropic hormone (ACTH) levels, these changes were not enough to reach significance. Similarly, there were no significant changes in catecholamine levels. This suggests that there is no significant impact of spaceflight on stress pathways. However, closer examination of the data indicates that the circadian rhythm may have masked the overall effect of spaceflight. http://dx.doi.org/10.1016/j.bbi.2014.06.048
29. Perceived stress and poor nutrition in individuals caring for family members with dementia, and controls, is associated with elevated serum cortisol and increased chromosomal instability C.F. Bull a,b, T. Almond a, H. Christensen c, M.F. Fenech a a CSIRO, Animal, Food & Health Sciences, Gate 13 Kintore Avenue, Adelaide, South Australia 5000, Australia b Molecular & Biomedical Sciences, University of Adelaide, South Australia, Australia c Black Dog Institute, Sydney, New South Wales, Australia
Chromosomal instability, arising from telomere dysfunction and DNA damage, is associated with degenerative diseases of ageing. Increased psychological stress has been consistently associated with shorter telomeres, which may explain its deleterious effects on health, but the causes of telomere shortening are not known. The aim of this study was to examine the interactive impact of nutritional status and chronic stress on chromosomal stability. We compared dietary intake, plasma micronutrient status, telomere length (flow cytometry) and DNA damage (micronuclei, biomarker of chromosome breakage or loss) in lymphocytes, stress hormones, and perceived stress (PSS) in individuals caring for a family member with dementia (n = 42), with age and gender matched non-carers (n = 42). Carers had significantly higher PSS, distress (both p < 0.0001), and anxiety (p = 0.0002) compared with controls. Telomere length (TL) was significantly (negatively) correlated with age (Pearson’s r = 0.5, p < 0.0001), and alcohol intake (r = 0.3, p = 0.006). Increased micronuclei were observed in participants with low serum folate (p = 0.07), high serum cortisol (p = 0.07) and perceived stress (p = 0.03). The highest quartile for PSS had the lowest serum folate concentrations (r = 0.4, p = 0.07), while elevated serum cortisol was associated with smoking, alcohol intake, and lower intake of dietary protein and five essential minerals (p = 0.01– 0.05). These data indicate that elevated stress, together with suboptimal nutrition, may impact on chromosomal stability, contrib-
e9
uting to increased morbidity, reduced immunity and accelerated ageing observed in chronically stressed individuals. http://dx.doi.org/10.1016/j.bbi.2014.06.049
30. Biome reconstitution as a novel mechanism of preventing neonatal infection-induced cognitive dysfunction L. Williamson, E. McKenney, W. Parker, S. Bilbo Duke University, Psychology & Neuroscience, GSRB-2, 572 Research Dr, Durham, NC 27710, USA The incidence of autoimmune and inflammatory diseases has risen in post-industrial societies. ‘‘Biome depletion’’ – loss of factors interacting with the immune system – may contribute to these increases. Helminths are commensalist organisms capable of modulating the immune system that have been lost in post-industrial society. Here, we investigated their therapeutic effects in a neonatal infection model known to cause cognitive impairments in adult rats. Breeders were given rat tapeworms (Hymenolepsis diminuta) or vehicle. The male offspring were injected with PBS or live Escherichia coli on postnatal day (PD) 4. At PD21, offspring were inoculated with tapeworms or vehicle, matching their mothers’ treatment. At PD65–70, rats were tested in a fear conditioning task, in which they received an injection of saline or LPS following context exploration/ learning. When tested for freezing behavior/memory, the ‘‘two hit’’ rats – those receiving E. coli on PD4 and LPS after learning – froze less, evidence of a significant memory deficit. However, helminthcolonized ‘‘two hit’’ rats demonstrated no cognitive impairment. Additionally, neonatally-infected pups sacrificed on PD5 had increased IL-1 mRNA within the hippocampus compared to PBS controls, whereas maternal helminth inoculation prevented this increase. The worms had no impact on adaptive immune cell subsets, whereas exaggerated innate inflammatory responses within cultured splenocytes were prevented. Together these data indicate that biome reconstitution is a viable preventative treatment for inflammation-induced cognitive impairments. http://dx.doi.org/10.1016/j.bbi.2014.06.050
31. Therapeutic morphine prolongs neuropathic pain in rats: A role for TLR4 and inflammasome signaling in the lumbar spinal cord P.M. Grace a, K.A. Strand a, E.L. Galer a, Y. Zhang a, D. Berkelhammer a, L.I. Greene a, K.C. Rice b, S.F. Maier a, L.R. Watkins a a Department of Psychology and the Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA b National Institute on Drug Abuse, USA
Microgliosis occurs after morphine and peripheral nerve injury alone, but the behavioral and molecular impact in tandem is unknown. We hypothesized that sciatic chronic constriction injury (CCI)-allodynia would be enhanced by subsequent repeated morphine in rats, involving TLR4, P2X7 receptor (P2X7R) and caspase1, facilitating release of interleukin (IL)-1b. Beginning 10 days after CCI, morphine (5 mg/kg b.i.d.) or saline was administered for 5 days. Compared to vehicle, morphine significantly prolonged the duration of CCI-induced allodynia (n = 6/group; p < 0.05). Morphine also significantly elevated TLR4 mRNA, P2X7R, NFkappaB, NLRP3 and caspase-1 protein levels (p < 0.05) in the ipsilateral lumbar dorsal quadrant (iLDQ), 5 weeks after dosing conclusion. Supporting a causal role for NLRP3 inflammasome activation in morphine-prolonged CCI-allodynia, continuous intrathecal infusion of inhibitors of TLR4
e10
Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52
([+]-naloxone; 60 micrograms/h), P2X7R (Brilliant Blue G; 30 ng/h), or caspase-1 (ac-YVAD-cmk; 1 lg/h) prevented prolonged allodynia when administered concomitantly with morphine, and abolished established morphine-prolonged CCI-allodynia when administered 5 weeks after morphine dosing (n = 6/group; p < 0.05). A single intrathecal IL-1 receptor antagonist dose (100 micrograms) also attenuated morphine-prolonged CCI-allodynia (n = 6/group; p < 0.05). In keeping with known pro-nociceptive roles for IL-1b, phosphorylation of the NR1 NMDA subunit was elevated, while GRK2 levels and GLT1 mRNA were decreased in iLDQ 5 weeks after dosing conclusion (p < 0.05). These data suggest that morphine and the products of nerve injury interact, resulting in prolonged neuropathic pain via sustained inflammasome signaling. http://dx.doi.org/10.1016/j.bbi.2014.06.051
32. Polarization to M1 microglia in high-anxiety inbred mice in response to LPS challenge Z. Li, L. Ma, N. Kulesskaya, V. Võikar, L. Tian Viikinkaari 4, Neuroscience Center, University of Helsinki, Helsinki 00790, Finland Objectives: Microglia play important roles in neurodevelopmental and pathological progression of mental disorders. But how genetic predisposition and environment risk factors may act in combination to affect microglial activation and the underlying molecular mechanisms remains unclear. Methods: Flow cytometry, RT-qPCR, and analysis of genome-wide brain transcriptomes, genotype–phenotype correlation, and gene functional clustering were employed to study the microglial profile both before and after LPS treatment across four inbred mice strains (C57BL/6J, FVB/N, DBA/2J, and 129S2/Sv) with different anxiety traits, and its relationship with anxiety traits and brain gene expression. Results: We found that naïve DBA/2J mice had significantly more M1 microglia. After a systemic LPS challenge, polarization to M1 microglia in DBA/2J and 129S2/ Sv mice was more prominent than the other strains, and was correlated with their anxiety-like behaviors. Macrophage M1/M2 polarization in the spleen showed a similar pattern in DBA/2J and 129S2/Sv mice in response to LPS challenge. Furthermore, DBA/2J mice expressed higher mRNA levels of Il1b, Il6, and Tnf, and higher Nos2/Arg1 ratio but lower Chi3l3 level in the hypothalamus before and after LPS stimulation, respectively. We further discovered a group of myeloid transcription factors that may underpin strain-specific differences in microglial activation. Conclusions: Proinflammatory microglial activation reflects anxiety traits in mice, especially after LPS challenge. Our work sheds new light in understanding the potential molecular mechanisms of stress-induced microglial activation and polarization. http://dx.doi.org/10.1016/j.bbi.2014.06.052
33. Longitudinal changes in serum proinflammatory markers across pregnancy and postpartum: Effects of maternal body mass index L.M. Christian, K. Porter The Ohio State University, Psychiatry, Institute for Behavioral Medicine Research, Room 112, Columbus, OH 43210, USA Background: The maternal immune system undergoes substantial changes to support healthy pregnancy. Although obesity
is a primary driver of inflammation and predictive of perinatal complications, additive effects of pregnancy and obesity on changes in inflammatory processes are not well delineated. Methods: This study examined serum proinflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-a, IL-1b, and C-reactive protein (CRP) during each trimester of pregnancy and 4–6 weeks postpartum among 57 women. Results: Overall, IL-6 showed an increasing trend across pregnancy and significant increase at postpartum. Similarly, TNF-a increased significantly across gestation, with a further increase at postpartum. Both IL-8 and IL-1b showed a U-shaped curve, decreasing from early to later pregnancy, and increasing at postpartum. Finally, serum CRP decreased significantly across pregnancy, with further decreases at postpartum. Maternal obesity predicted higher IL-6 at each study visit. Obese women showed a trend toward elevated serum CRP during pregnancy, and significantly higher levels at postpartum. Discussion: The course of pregnancy and postpartum is characterized by significant changes in serum proinflammatory mediators. Obese women show elevations in serum proinflammatory markers relative to normal weight women during pregnancy and postpartum. Further research is needed to determine the extent to which obesity-induced inflammation affects maternal and fetal health. http://dx.doi.org/10.1016/j.bbi.2014.06.053
34. Gene polymorphisms of stress hormone receptors and cytokine receptors associate with immunomodulatory profile and psychological measurements L. Xiang, K. Rehm, I. Sunesara, M. Griswold, G.D. Marshall Jr. 2500 North State Street, Laboratory of Behavioral Immunology Research, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA The association between psychological stress and immune response has been firmly established, but prospectively identifying individual stress susceptibility is difficult. We sought to identify stable single nucleotide polymorphism (SNP) biomarkers that could predict specific immune alterations association with chronic stress measures (PSS, STAI, BDI) in humans. 207 normal participants answered stress questionnaires and gave peripheral blood (PBMC) for identification of SNPs in genes coding for glucocorticoid receptor (GR), beta 2-adrenergic receptor (B2AR), interferon-c receptors (IFNGR1, IFNGR2), interleukin4 receptor (IL4R) and quantitation of Th1 and Th2 cells by flow cytometry. Results showed several significant differences in relationships between stress markers and immune indicators based upon SNP categories including positive correlation of Th1 with PSS in minor allele (AA) of GR TthIIII and minor allele (Arg/Arg) of IFNGR2 Q64R compared to wild type (WT), negative correlation of Th2 with BDI in minor allele (GG) of GR BclI compared to WT and negative correlation of Th1/Th2 ratio with BDI in minor allele (Glu/Glu) of B2AR Gln27Glu compared to WT. We conclude that gene polymorphisms from various components of the stress-immune network may be useful as biomarkers to categorize and possibly predict individual stress-associated immune responses. This approach has significant clinical potential in identifying those patients who may be most susceptible to stress effects on their immune balance. http://dx.doi.org/10.1016/j.bbi.2014.06.054
In previous experiments, we have shown that spaceflight can alter leukocyte and lymphocyte population distributions and mitogen-induced cytokine expression. We hypothesize that these changes are a result of flight-induced physiological and psychological stress. On July 8, 2011, age- and weight-matched, female C57BL/6J mice were placed into Animal Enclosure Modules (AEMs) and flown on the Space Shuttle Atlantis (STS-135) for 13 days (N = 6–7). Ground controls were housed at the Space Life Science Laboratory (SLSL) at Kennedy Space Center (KSC). Ground AEM control mice were placed into the same hardware used in flight and environmental parameters such as temperature and CO2 levels were matched as closely as possible based on 48 h delayed telemetry data (N = 12–13). Vivarium control mice were housed in regular shoebox cages (N = 4). Mice were euthanized and dissected within 3–5 h of landing. Adrenals were removed, snap frozen in liquid N2, and shipped on ice back to Loma Linda University via overnight courier for analysis. Although corticosterone levels were slightly elevated in spaceflight mice, with a corresponding decrease in phosphorylated adrenocorticotropic hormone (ACTH) levels, these changes were not enough to reach significance. Similarly, there were no significant changes in catecholamine levels. This suggests that there is no significant impact of spaceflight on stress pathways. However, closer examination of the data indicates that the circadian rhythm may have masked the overall effect of spaceflight. http://dx.doi.org/10.1016/j.bbi.2014.06.048
29. Perceived stress and poor nutrition in individuals caring for family members with dementia, and controls, is associated with elevated serum cortisol and increased chromosomal instability C.F. Bull a,b, T. Almond a, H. Christensen c, M.F. Fenech a a CSIRO, Animal, Food & Health Sciences, Gate 13 Kintore Avenue, Adelaide, South Australia 5000, Australia b Molecular & Biomedical Sciences, University of Adelaide, South Australia, Australia c Black Dog Institute, Sydney, New South Wales, Australia
Chromosomal instability, arising from telomere dysfunction and DNA damage, is associated with degenerative diseases of ageing. Increased psychological stress has been consistently associated with shorter telomeres, which may explain its deleterious effects on health, but the causes of telomere shortening are not known. The aim of this study was to examine the interactive impact of nutritional status and chronic stress on chromosomal stability. We compared dietary intake, plasma micronutrient status, telomere length (flow cytometry) and DNA damage (micronuclei, biomarker of chromosome breakage or loss) in lymphocytes, stress hormones, and perceived stress (PSS) in individuals caring for a family member with dementia (n = 42), with age and gender matched non-carers (n = 42). Carers had significantly higher PSS, distress (both p < 0.0001), and anxiety (p = 0.0002) compared with controls. Telomere length (TL) was significantly (negatively) correlated with age (Pearson’s r = 0.5, p < 0.0001), and alcohol intake (r = 0.3, p = 0.006). Increased micronuclei were observed in participants with low serum folate (p = 0.07), high serum cortisol (p = 0.07) and perceived stress (p = 0.03). The highest quartile for PSS had the lowest serum folate concentrations (r = 0.4, p = 0.07), while elevated serum cortisol was associated with smoking, alcohol intake, and lower intake of dietary protein and five essential minerals (p = 0.01– 0.05). These data indicate that elevated stress, together with suboptimal nutrition, may impact on chromosomal stability, contrib-
e9
uting to increased morbidity, reduced immunity and accelerated ageing observed in chronically stressed individuals. http://dx.doi.org/10.1016/j.bbi.2014.06.049
30. Biome reconstitution as a novel mechanism of preventing neonatal infection-induced cognitive dysfunction L. Williamson, E. McKenney, W. Parker, S. Bilbo Duke University, Psychology & Neuroscience, GSRB-2, 572 Research Dr, Durham, NC 27710, USA The incidence of autoimmune and inflammatory diseases has risen in post-industrial societies. ‘‘Biome depletion’’ – loss of factors interacting with the immune system – may contribute to these increases. Helminths are commensalist organisms capable of modulating the immune system that have been lost in post-industrial society. Here, we investigated their therapeutic effects in a neonatal infection model known to cause cognitive impairments in adult rats. Breeders were given rat tapeworms (Hymenolepsis diminuta) or vehicle. The male offspring were injected with PBS or live Escherichia coli on postnatal day (PD) 4. At PD21, offspring were inoculated with tapeworms or vehicle, matching their mothers’ treatment. At PD65–70, rats were tested in a fear conditioning task, in which they received an injection of saline or LPS following context exploration/ learning. When tested for freezing behavior/memory, the ‘‘two hit’’ rats – those receiving E. coli on PD4 and LPS after learning – froze less, evidence of a significant memory deficit. However, helminthcolonized ‘‘two hit’’ rats demonstrated no cognitive impairment. Additionally, neonatally-infected pups sacrificed on PD5 had increased IL-1 mRNA within the hippocampus compared to PBS controls, whereas maternal helminth inoculation prevented this increase. The worms had no impact on adaptive immune cell subsets, whereas exaggerated innate inflammatory responses within cultured splenocytes were prevented. Together these data indicate that biome reconstitution is a viable preventative treatment for inflammation-induced cognitive impairments. http://dx.doi.org/10.1016/j.bbi.2014.06.050
31. Therapeutic morphine prolongs neuropathic pain in rats: A role for TLR4 and inflammasome signaling in the lumbar spinal cord P.M. Grace a, K.A. Strand a, E.L. Galer a, Y. Zhang a, D. Berkelhammer a, L.I. Greene a, K.C. Rice b, S.F. Maier a, L.R. Watkins a a Department of Psychology and the Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA b National Institute on Drug Abuse, USA
Microgliosis occurs after morphine and peripheral nerve injury alone, but the behavioral and molecular impact in tandem is unknown. We hypothesized that sciatic chronic constriction injury (CCI)-allodynia would be enhanced by subsequent repeated morphine in rats, involving TLR4, P2X7 receptor (P2X7R) and caspase1, facilitating release of interleukin (IL)-1b. Beginning 10 days after CCI, morphine (5 mg/kg b.i.d.) or saline was administered for 5 days. Compared to vehicle, morphine significantly prolonged the duration of CCI-induced allodynia (n = 6/group; p < 0.05). Morphine also significantly elevated TLR4 mRNA, P2X7R, NFkappaB, NLRP3 and caspase-1 protein levels (p < 0.05) in the ipsilateral lumbar dorsal quadrant (iLDQ), 5 weeks after dosing conclusion. Supporting a causal role for NLRP3 inflammasome activation in morphine-prolonged CCI-allodynia, continuous intrathecal infusion of inhibitors of TLR4
e10
Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52
([+]-naloxone; 60 micrograms/h), P2X7R (Brilliant Blue G; 30 ng/h), or caspase-1 (ac-YVAD-cmk; 1 lg/h) prevented prolonged allodynia when administered concomitantly with morphine, and abolished established morphine-prolonged CCI-allodynia when administered 5 weeks after morphine dosing (n = 6/group; p < 0.05). A single intrathecal IL-1 receptor antagonist dose (100 micrograms) also attenuated morphine-prolonged CCI-allodynia (n = 6/group; p < 0.05). In keeping with known pro-nociceptive roles for IL-1b, phosphorylation of the NR1 NMDA subunit was elevated, while GRK2 levels and GLT1 mRNA were decreased in iLDQ 5 weeks after dosing conclusion (p < 0.05). These data suggest that morphine and the products of nerve injury interact, resulting in prolonged neuropathic pain via sustained inflammasome signaling. http://dx.doi.org/10.1016/j.bbi.2014.06.051
32. Polarization to M1 microglia in high-anxiety inbred mice in response to LPS challenge Z. Li, L. Ma, N. Kulesskaya, V. Võikar, L. Tian Viikinkaari 4, Neuroscience Center, University of Helsinki, Helsinki 00790, Finland Objectives: Microglia play important roles in neurodevelopmental and pathological progression of mental disorders. But how genetic predisposition and environment risk factors may act in combination to affect microglial activation and the underlying molecular mechanisms remains unclear. Methods: Flow cytometry, RT-qPCR, and analysis of genome-wide brain transcriptomes, genotype–phenotype correlation, and gene functional clustering were employed to study the microglial profile both before and after LPS treatment across four inbred mice strains (C57BL/6J, FVB/N, DBA/2J, and 129S2/Sv) with different anxiety traits, and its relationship with anxiety traits and brain gene expression. Results: We found that naïve DBA/2J mice had significantly more M1 microglia. After a systemic LPS challenge, polarization to M1 microglia in DBA/2J and 129S2/ Sv mice was more prominent than the other strains, and was correlated with their anxiety-like behaviors. Macrophage M1/M2 polarization in the spleen showed a similar pattern in DBA/2J and 129S2/Sv mice in response to LPS challenge. Furthermore, DBA/2J mice expressed higher mRNA levels of Il1b, Il6, and Tnf, and higher Nos2/Arg1 ratio but lower Chi3l3 level in the hypothalamus before and after LPS stimulation, respectively. We further discovered a group of myeloid transcription factors that may underpin strain-specific differences in microglial activation. Conclusions: Proinflammatory microglial activation reflects anxiety traits in mice, especially after LPS challenge. Our work sheds new light in understanding the potential molecular mechanisms of stress-induced microglial activation and polarization. http://dx.doi.org/10.1016/j.bbi.2014.06.052
33. Longitudinal changes in serum proinflammatory markers across pregnancy and postpartum: Effects of maternal body mass index L.M. Christian, K. Porter The Ohio State University, Psychiatry, Institute for Behavioral Medicine Research, Room 112, Columbus, OH 43210, USA Background: The maternal immune system undergoes substantial changes to support healthy pregnancy. Although obesity
is a primary driver of inflammation and predictive of perinatal complications, additive effects of pregnancy and obesity on changes in inflammatory processes are not well delineated. Methods: This study examined serum proinflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-a, IL-1b, and C-reactive protein (CRP) during each trimester of pregnancy and 4–6 weeks postpartum among 57 women. Results: Overall, IL-6 showed an increasing trend across pregnancy and significant increase at postpartum. Similarly, TNF-a increased significantly across gestation, with a further increase at postpartum. Both IL-8 and IL-1b showed a U-shaped curve, decreasing from early to later pregnancy, and increasing at postpartum. Finally, serum CRP decreased significantly across pregnancy, with further decreases at postpartum. Maternal obesity predicted higher IL-6 at each study visit. Obese women showed a trend toward elevated serum CRP during pregnancy, and significantly higher levels at postpartum. Discussion: The course of pregnancy and postpartum is characterized by significant changes in serum proinflammatory mediators. Obese women show elevations in serum proinflammatory markers relative to normal weight women during pregnancy and postpartum. Further research is needed to determine the extent to which obesity-induced inflammation affects maternal and fetal health. http://dx.doi.org/10.1016/j.bbi.2014.06.053
34. Gene polymorphisms of stress hormone receptors and cytokine receptors associate with immunomodulatory profile and psychological measurements L. Xiang, K. Rehm, I. Sunesara, M. Griswold, G.D. Marshall Jr. 2500 North State Street, Laboratory of Behavioral Immunology Research, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA The association between psychological stress and immune response has been firmly established, but prospectively identifying individual stress susceptibility is difficult. We sought to identify stable single nucleotide polymorphism (SNP) biomarkers that could predict specific immune alterations association with chronic stress measures (PSS, STAI, BDI) in humans. 207 normal participants answered stress questionnaires and gave peripheral blood (PBMC) for identification of SNPs in genes coding for glucocorticoid receptor (GR), beta 2-adrenergic receptor (B2AR), interferon-c receptors (IFNGR1, IFNGR2), interleukin4 receptor (IL4R) and quantitation of Th1 and Th2 cells by flow cytometry. Results showed several significant differences in relationships between stress markers and immune indicators based upon SNP categories including positive correlation of Th1 with PSS in minor allele (AA) of GR TthIIII and minor allele (Arg/Arg) of IFNGR2 Q64R compared to wild type (WT), negative correlation of Th2 with BDI in minor allele (GG) of GR BclI compared to WT and negative correlation of Th1/Th2 ratio with BDI in minor allele (Glu/Glu) of B2AR Gln27Glu compared to WT. We conclude that gene polymorphisms from various components of the stress-immune network may be useful as biomarkers to categorize and possibly predict individual stress-associated immune responses. This approach has significant clinical potential in identifying those patients who may be most susceptible to stress effects on their immune balance. http://dx.doi.org/10.1016/j.bbi.2014.06.054