A distinct immune cytokine profile is associated with morning cortisol and repeated stress
DOI:
https://doi.org/10.5055/ajdm.0468Keywords:
stress, cytokines, mass casualty, simulation training, immune responseAbstract
Objective: The objective of this study was to investigate possible immune cytokine trends throughout a week-long surgical simulation mass-casualty training session in order to determine the effects of stress inoculation on the immune system.
Methods: Thirty-seven military medical students participated in a hyper-realistic surgical simulation training event conducted at Strategic Operations site in San Diego, California. Salivary samples were collected every morning of the stress training exercise for 4 consecutive days. Cortisol, along with a panel of 42 immune cytokines, was measured using multiplex enzyme-linked immunosorbent assays from Eve Technologies. The determined concentrations were averaged and plotted on a scatter plot, and then points were fit to a second-order polynomial trendline of best fit to measure.
Results: The cytokines epidermal growth factor, growth-related oncogene-α, interleukin (IL)-1α, and platelet-derived growth factor-AA followed a noted pattern of cortisol decrease throughout the week. In addition, cytokines IL-27, granulocyte colony stimulating factor, IL-10, and IL-13 demonstrated a late peak, followed by a return to baseline at the conclusion of training. Finally, the cytokine monocyte chemoattractant protein-1 displayed a decline throughout the week followed by an increase on the last day of stress training.
Conclusions: Altogether, these results help to identify important biomarkers that may help to improve long-term stress adaptation and prevent post-traumatic stress disorder following exposure to repeated stress.
References
Morey JN, Boggero IA, Scott AB, et al.: Current directions in stress and human immune function. Curr Opin Psychol. 2015; 5: 13-17. DOI: 10.1016/j.copsyc.2015.03.007. DOI: https://doi.org/10.1016/j.copsyc.2015.03.007
Salleh MR: Life event, stress and illness. Malays J Med Sci. 2008; 15(4): 9-18.
Bellavance MA, Rivest S: The HPA—Immune axis and the immunomodulatory actions of glucocorticoids in the brain. Front Immunol. 2014; 5: 136. DOI: 10.3389/fimmu.2014.00136. DOI: https://doi.org/10.3389/fimmu.2014.00136
Menard C, Pfau M, Hodes G, et al.: Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropsychopharmacology. 2017; 42: 62-80. DOI: 10.1038/npp.2016.90. DOI: https://doi.org/10.1038/npp.2016.90
Boggero I, Hostinar C, Haak E, et al.: Psychosocial functioning and the cortisol awakening response: Meta-analysis, P-curve analysis, and evaluation of the evidential value in existing studies. Biol Psychol. 2017; 129: 207-230. DOI: 10.1016/j.biopsycho.2017.08.058. DOI: https://doi.org/10.1016/j.biopsycho.2017.08.058
Powell DJ, Schlotz W: Daily life stress and the cortisol awakening response: Testing the anticipation hypothesis. PLoS One. 2012; 7(12): E52067. DOI: https://doi.org/10.1371/journal.pone.0052067
McEwen BS, Nasca C, Gray JD: Stress effects on neuronal structure: Hippocampus, amygdala, and prefrontal cortex. Neuropsychopharmacology. 2016; 41(1): 3-23. DOI: 10.1038/npp.2015.171. DOI: https://doi.org/10.1038/npp.2015.171
Hoang TN, LaPorta AJ, Malone JD, et al.: Hyper-realistic and immersive surgical simulation training environment will improve team performance, trauma surg. Trauma Surg Acute Care Open. 2020; 5: E000393. DOI: 10.1136/tsaco-2019-000393. DOI: https://doi.org/10.1136/tsaco-2019-000393
LaPorta AJ, McKee J, Hoang T, et al.: Stress inoculation: Preparing outside the box in surgical resuscitation and education. Curr Trauma Rep. 2017. DOI: 10.1007/s40719-017-0090-2. DOI: https://doi.org/10.1007/s40719-017-0090-2
Zapata I, Farrell J, Morrell S, et al.: Emotional intelligence, cortisol and α-amylase response to highly stressful hyper-realistic surgical simulation of a mass casualty event scenario. Compr Psychoneuroendocrinol. 2021; 5: 100031. DOI: 10.1016/J.CPNEC.2021.100031. DOI: https://doi.org/10.1016/j.cpnec.2021.100031
Ryznar R, Wong C, Onat E, et al.: Principal component analysis of salivary cytokines and hormones in the acute stress response. Front Psychiatry. 2022; 13: 957545. DOI: 10.3389/fpsyt.2022.957545. DOI: https://doi.org/10.3389/fpsyt.2022.957545
Lai JCL, Leung MOY, Lee DYH, et al.: Biomarking trait resilience with salivary cortisol in Chinese undergraduates. Front Psychol. 2020; 11: 536510. DOI: 10.3389/fpsyg.2020.536510. DOI: https://doi.org/10.3389/fpsyg.2020.536510
Yeager MP, Pioli PA, Guyre PM: Cortisol exerts bi-phasic regulation of inflammation in humans. Dose Response. 2011; 9(3): 1-347. DOI: 10.2203/dose-response.10-013. DOI: https://doi.org/10.2203/dose-response.10-013.Yeager
Berlanga-Acosta J, Gavilondo-Cowley J, Lopez-Saura P, et al.: Epidermal growth factor in clinical practice—A review of its biological actions, clinical indications and safety implications. Int Wound J. 2009; 6(5): 331-346. DOI: 10.1111/j.1742-481X.2009.00622.x. DOI: https://doi.org/10.1111/j.1742-481X.2009.00622.x
Herbst RS: Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys. 2004; 59(2): 21-26. DOI: https://doi.org/10.1016/j.ijrobp.2003.11.041
Asberg M, Nygren A, Leopardi R, et al.: Novel biochemical markers of psychosocial stress in women. PLoS One. 2009; 4(1): E3590. DOI: 10.1371/journal.pone.0003590. DOI: https://doi.org/10.1371/journal.pone.0003590
Zhang Q, Liu G, Wu Y, et al.: BDNF promotes EGF-induced proliferation and migration of human fetal neural stem/progenitor cells via the PI3K/akt pathway. Molecules. 2011; 16(12): 10146-10156. DOI: 10.3390/molecules161210146. DOI: https://doi.org/10.3390/molecules161210146
Cohen I, Rider P, Vornov E, et al.: IL-1α is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity. Sci Rep. 2015; 5: 14756. DOI: 10.1038/srep14756. DOI: https://doi.org/10.1038/srep14756
Pearson-Leary J, Eacret D, Bhatnagar S: Interleukin-1α in the ventral hippocampus increases stress vulnerability and inflammation-related processes. Stress. 2020; 23(3): 308-317. DOI: 10.1080/10253890.2019.1673360. DOI: https://doi.org/10.1080/10253890.2019.1673360
Lee DY, Kim E, Choi MH: Technical and clinical aspects of cortisol as a biochemical marker of chronic stress. BMB Rep. 2015; 48(4): 209-216. DOI: 10.5483/bmbrep.2015.48.4.275. DOI: https://doi.org/10.5483/BMBRep.2015.48.4.275
Long KLP, Chao LL, Kazama Y, et al.: Regional gray matter oligodendrocyte-and myelin-related measures are associated with differential susceptibility to stress-induced behavior in rats and humans. Transl Psychiatry. 2021; 11: 631. DOI: 10.1038/s41398-021-01745-5. DOI: https://doi.org/10.1038/s41398-021-01745-5
Tang L, Cai N, Zhou Y, et al.: Acute stress induces an inflammation dominated by innate immunity represented by neutrophils in mice. Front Immunol. 2022; 13: 1014296. DOI: 10.3389/fimmu.2022.1014296. DOI: https://doi.org/10.3389/fimmu.2022.1014296
Abdalla AE, Li Q, Xie L, et al.: Biology of IL-27 and its role in the host immunity against mycobacterium tuberculosis. Int J Biol Sci. 2015; 11(2): 168-175. DOI: 10.7150/ijbs.10464. DOI: https://doi.org/10.7150/ijbs.10464
Rudak PT, Choi J, Parkins KM, et al.: Chronic stress physically spares but functionally impairs innate-like invariant T cells. Cell Rep. 2021; 35(2): 108979. DOI: 10.1016/j.celrep.2021.108979. DOI: https://doi.org/10.1016/j.celrep.2021.108979
Ambree O, Ruland C, Zwanzger P, et al.: Social defeat modulates T helper cell percentages in stress susceptible and resilient mice. Int J Mol Sci. 2019; 20(14): 3512. DOI: 10.3390/ijms20143512. DOI: https://doi.org/10.3390/ijms20143512
Li H, Linjuan L, Wang Y: G-CSF improves CUMS-induced depressive behaviors through downregulating ras/ERK/MAPK signaling pathway. Biochem Biophys Res Commun. 2016; 479(4): 827-832. DOI: 10.1016/j.bbrc.2016.09.123. DOI: https://doi.org/10.1016/j.bbrc.2016.09.123
Szabo YZ, Newton TL, Miller JJ, et al.: Acute stress induces increases in salivary IL-10 levels. Stress. 2016; 19(5): 499-505. DOI: https://doi.org/10.1080/10253890.2016.1206885
Kim C, Schinkel C, Fuchs D, et al.: Interleukin-13 effectively down-regulates the monocyte inflammatory potential during traumatic stress. Arch Surg. 1995; 130(12): 1330-1336. DOI: https://doi.org/10.1001/archsurg.1995.01430120084013
Tian R, Hou G, Li D, et al.: A possible change process of inflammatory cytokines in the prolonged chronic stress and its ultimate implications for health. Sci World J. 2014; 2014: 1-8. DOI: 10.1155/2014/780616. DOI: https://doi.org/10.1155/2014/780616
Priyadarshini S, Aich P: Effects of psychological stress on innate immunity and metabolism in humans: A systematic analysis. PLoS One. 2012; 7(9): e43232. DOI: 10.1371/journal.pone.0043232. DOI: https://doi.org/10.1371/journal.pone.0043232
Madrigal JL, Garcia-Bueno B, Hinojosa AE, et al.: Regulation of MCP-1 production in brain by stress and noradrenaline-modulating drugs. J Neurochem. 2010; 113(2): 543-551. DOI: 10.1111/j.1471-4159.2010.06623.x. DOI: https://doi.org/10.1111/j.1471-4159.2010.06623.x
West E, Singer-Chang G, Ryznar R, et al.: The effect of hyper-realistic trauma training on emotional intelligence in second year military medical students. J Surg Educ. 2020; 77(6): 1422-1428. DOI: https://doi.org/10.1016/j.jsurg.2020.04.020
Dhabhar FS, Malarkey WB, Neri E, et al.: Stress-induced redistribution of immune cells—From barracks to boulevards to battlefields: A tale of three hormones–Curt Richter award winner. Psychoneuroendocrinology. 2012; 37(9): 1345-1368. DOI: https://doi.org/10.1016/j.psyneuen.2012.05.008
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