Inflammatory reactivity to the influenza vaccine is associated with changes in automatic social behavior

Tatum A Jolink, Nicholas J Fendinger, Gabriella M Alvarez, Mallory J Feldman, Monica M Gaudier-Diaz, Keely A Muscatell, Tatum A Jolink, Nicholas J Fendinger, Gabriella M Alvarez, Mallory J Feldman, Monica M Gaudier-Diaz, Keely A Muscatell

Abstract

Recent evidence suggests differential patterns of social behavior following an inflammatory challenge, such that increases in inflammation may not uniformly lead to social withdrawal. Indeed, increases in inflammation have been associated with enhanced self-reported motivation to approach a specific close other, and greater neural sensitivity to positive social cues. However, no known studies have examined the association between inflammation in response to an inflammatory challenge and social behavior in humans, nor has past research examined specifically how approach and withdrawal behavior may differ based on whether the target is a close other or stranger. To address this, 31 participants (ages 18-24) received the influenza vaccine to elicit a low-grade inflammatory response. The morning before and approximately 24 h after the vaccine, participants provided a blood sample and completed a computer task assessing automatic (implicit) approach and withdrawal behavior toward a social support figure and strangers. Greater increases in the inflammatory cytokine interleukin-6 (IL-6) in response to the vaccine were associated with an increase in accuracy in avoiding strangers and a decrease in accuracy in approaching them. Increases in IL-6 were also associated with a decrease in reaction time to approach a support figure, but only when controlling for baseline IL-6 levels. There were no associations between change in IL-6 and changes in self-reported motivation to engage in social behavior with either close others, or strangers. Together, these findings reveal that increases in inflammation following the influenza vaccine are associated with automatic social behavior, especially behavior suggesting avoidance of unfamiliar social targets and ease in approaching a support figure. These data add to the growing literature suggesting that the association between inflammation and social behavior includes both social withdrawal and social approach, depending on the specific target.

Keywords: Close relationships; Inflammation; Influenza vaccine; Interleukin-6; Social approach; Social behavior; Social withdrawal.

Copyright © 2021 Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Note. IL-6 levels at pre-vaccine and post-vaccine administration for each participant based on raw (not log-transformed) IL-6 values. Box and whisker plots depict the mean and distribution of IL-6 scores for both pre-vaccine (left-side) and post-vaccine (right-side).
Figure 2
Figure 2
Note. Within-subject change in latency approaching support figure from pre-vaccine to post-vaccine predicted by within-subject change in IL-6. Model adjusted for sex, BMI, relationship type, and pre-vaccine IL-6.
Figure 3
Figure 3
Note. Within-subject change in accuracy approaching strangers (a) and withdrawing from strangers (b) from pre-vaccine to post-vaccine predicted by within-subject change in IL-6 from pre-vaccine to post-vaccine. Models adjusted for sex and BMI.

References

    1. Aubert A, Goodall G, Dantzer R, Gheusi G. Differential effects of lipopolysaccharide on pup retrieving and nest building in lactating mice. Brain Behav Immun. 1997;11(2):107–118. doi:10.1006/brbi.1997.0485
    1. Aubert A. Sickness and behaviour in animals: a motivational perspective. Neurosci Biobehav Rev. 1999;23(7):1029–1036. doi:10.1016/s0149-7634(99)00034-2
    1. Barkby H, Dickson JM, Roper L, Field M. To approach or avoid alcohol? Automatic and selfreported motivational tendencies in alcohol dependence. Alcohol Clin Exp Res. 2012;36(2):361–368. doi:10.1111/j.1530-0277.2011.01620.x
    1. Bernstein MJ, Claypool HM, Nadzan MA, Schuepfer K, Benfield JA, Nutt RJ. Validating the state motivation to foster social connections scale. J Soc Psychol. 2019;159(6):709–724. doi:10.1080/00224545.2018.1558882
    1. Bilbo SD, Klein SL, DeVries AC, Nelson RJ. Lipopolysaccharide facilitates partner preference behaviors in female prairie voles. Physiol Behav. 1999;68(1–2):151–156. doi:10.1016/s0031-9384(99)00154-7
    1. Bluthé RM, Michaud B, Kelley KW, Dantzer R. Vagotomy attenuates behavioural effects of interleukin-1 injected peripherally but not centrally. Neuroreport. 1996;7(9):1485–1488. doi:10.1097/00001756-199606170-00008
    1. Bluthé RM, Walter V, Parnet P, et al. Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C R Acad Sci III. 1994;317(6):499–503.
    1. Boyle CC, Kuhlman KR, Dooley LN, et al. Inflammation and dimensions of reward processing following exposure to the influenza vaccine. Psychoneuroendocrinology. 2019;102:16–23. doi:10.1016/j.psyneuen.2018.11.024
    1. Brydon L, Harrison NA, Walker C, Steptoe A, Critchley HD. Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biol Psychiatry. 2008;63(11):1022–1029. doi:10.1016/j.biopsych.2007.12.007
    1. Carty CL, Heagerty P, Nakayama K, et al. Inflammatory response after influenza vaccination in men with and without carotid artery disease. Arterioscler Thromb Vasc Biol. 2006;26(12):2738–2744. doi:10.1161/01.ATV.0000248534.30057.b5
    1. Christian LM, Iams JD, Porter K, Glaser R. Inflammatory responses to trivalent influenza virus vaccine among pregnant women. Vaccine. 2011;29(48):8982–8987. doi:10.1016/j.vaccine.2011.09.039
    1. Christian LM, Porter K, Karlsson E, Schultz-Cherry S, Iams JD. Serum proinflammatory cytokine responses to influenza virus vaccine among women during pregnancy versus non-pregnancy. Am J Reprod Immunol. 2013;70(1):45–53. doi:10.1111/aji.12117
    1. Cohen S, Alper CM, Doyle WJ, Treanor JJ, Turner RB. Positive emotional style predicts resistance to illness after experimental exposure to rhinovirus or influenza A virus. Psychosom Med. 2006;68:809–815. doi:10.1097/01.psy.0000245867.92364.3c
    1. Cole SW. The complexity of dynamic host networks. In: Deisboeck TS, Kresh JY, editors. Complex Systems Science in BioMedicine. New York: Kluwer Academic; 2006. pp. 605–629.
    1. Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun. 2007;21(2):153–160. doi:10.1016/j.bbi.2006.09.006
    1. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9(1):46–56. doi:10.1038/nrn2297
    1. Dantzer R. Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci. 2001;933:222–234. doi:10.1111/j.1749-6632.2001.tb05827.x
    1. De Houwer J, Crombez G, Baeyens F, Hermans D. On the generality of the affective Simon effect. Cogn Emot. 2001;15: 189–206.
    1. Dewitte M, De Houwer J, Buysse A, Koster EH. Proximity seeking in adult attachment: examining the role of automatic approach-avoidance tendencies. Br J Soc Psychol. 2008;47(Pt 4):557–573. doi:10.1348/014466607X265148
    1. Eisenberger NI, Inagaki TK, Mashal NM, Irwin MR. Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Brain Behav Immun. 2010;24(4):558–563. doi:10.1016/j.bbi.2009.12.009
    1. Eisenberger NI, Inagaki TK, Rameson LT, Mashal NM, Irwin MR. An fMRI study of cytokineinduced depressed mood and social pain: the role of sex differences. Neuroimage. 2009;47(3):881–890. doi:10.1016/j.neuroimage.2009.04.040
    1. Eisenberger NI, Moieni M, Inagaki TK, Muscatell KA, Irwin MR. In Sickness and in Health: The Co-Regulation of Inflammation and Social Behavior. Neuropsychopharmacology. 2017;42(1):242–253. doi:10.1038/npp.2016.141
    1. Field M, Caren R, Fernie G, De Houwer J. Alcohol approach tendencies in heavy drinkers: comparison of effects in a Relevant Stimulus-Response Compatibility task and an approach/avoidance Simon task. Psychol Addict Behav. 2011;25(4):697–701. doi:10.1037/a0023285
    1. Field M, Eastwood B, Bradley BP, Mogg K. Selective processing of cannabis cues in regular cannabis users. Drug Alcohol Depend. 2006;85(1):75–82. doi:10.1016/j.drugalcdep.2006.03.018
    1. Field M, Mogg K, Bradley BP. Craving and cognitive biases for alcohol cues in social drinkers. Alcohol Alcohol. 2005;40(6):504–510. doi:10.1093/alcalc/agh213
    1. Field M, Mogg K, Zetteler J, Bradley BP. Attentional biases for alcohol cues in heavy and light social drinkers: the roles of initial orienting and maintained attention. Psychopharmacology (Berl). 2004;176(1):88–93. doi:10.1007/s00213-004-1855-1
    1. Gassen J, Hill SE. Why inflammation and the activities of the immune system matter for social and personality psychology (and not only for those who study health). Soc Personal Psychol Compass. 2019;13(6). doi:10.1111/spc3.12471.
    1. Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry. 2009;66(5):407–414. doi:10.1016/j.biopsych.2009.03.015
    1. Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev. 1988;12(2):123–137. doi:10.1016/s0149-7634(88)80004-6
    1. Hennessy MB, Deak T, Schiml PA. Sociality and sickness: have cytokines evolved to serve social functions beyond times of pathogen exposure?. Brain Behav Immun. 2014;37:15–20. doi:10.1016/j.bbi.2013.10.021
    1. Inagaki TK, Muscatell KA, Irwin MR, Cole SW, Eisenberger NI. Inflammation selectively enhances amygdala activity to socially threatening images. Neuroimage. 2012;59(4):3222–3226. doi:10.1016/j.neuroimage.2011.10.090
    1. Inagaki TK, Muscatell KA, Irwin MR, et al. The role of the ventral striatum in inflammatoryinduced approach toward support figures. Brain Behav Immun. 2015;44:247–252. doi:10.1016/j.bbi.2014.10.006
    1. Kawakami K, Phills CE, Steele JR, Dovidio JF. (Close) distance makes the heart grow fonder:Improving implicit racial attitudes and interracial interactions through approach behaviors. J Pers Soc Psychol. 2007;92(6):957–971. doi:10.1037/0022-3514.92.6.957
    1. Kelley KW, Bluthé RM, Dantzer R, et al. Cytokine-induced sickness behavior. Brain Behav Immun. 2003;17 Suppl 1:S112–S118. doi:10.1016/s0889-1591(02)00077-6
    1. Kuhlman KR, Robles TF, Dooley LN, Boyle CC, Haydon MD, Bower JE. Within-subject associations between inflammation and features of depression: Using the flu vaccine as a mild inflammatory stimulus. Brain Behav Immun. 2018;69:540–547. doi:10.1016/j.bbi.2018.02.001
    1. Kuhlman KR, Robles TF, Haydon MD, Dooley L, Boyle CC, Bower JE. Early life stress sensitizes individuals to the psychological correlates of mild fluctuations in inflammation. Dev Psychobiol. 2020;62(3):400–408. doi:10.1002/dev.21908
    1. Kullmann JS, Grigoleit JS, Wolf OT, et al. Experimental human endotoxemia enhances brain activity during social cognition. Soc Cogn Affect Neurosci. 2014;9(6):786–793. doi:10.1093/scan/nst049
    1. Larson SJ, Dunn AJ. Behavioral effects of cytokines. Brain Behav Immun. 2001;15(4):371–387. doi:10.1006/brbi.2001.0643
    1. Lindsay EK, Inagaki TK, Walsh C, Messay B, Ewing L, Marsland A. Stress-related inflammation and social withdrawal in mothers after childhood cancer diagnosis. doi:10.31234/.
    1. Marvel FA, Chen CC, Badr N, Gaykema RP, Goehler LE. Reversible inactivation of the dorsal vagal complex blocks lipopolysaccharide-induced social withdrawal and c-Fos expression in central autonomic nuclei. Brain Behav Immun. 2004;18(2):123–134. doi:10.1016/j.bbi.2003.09.004
    1. Mogg K, Bradley BP, Field M, De Houwer J. Eye movements to smoking-related pictures in smokers: relationship between attentional biases and implicit and explicit measures of stimulus valence. Addiction. 2003;98(6):825–836. doi:10.1046/j.1360-0443.2003.00392.x
    1. Moieni M, Irwin MR, Jevtic I, Olmstead R, Breen EC, Eisenberger NI. Sex differences in depressive and socioemotional responses to an inflammatory challenge: implications for sex differences in depression. Neuropsychopharmacology. 2015;40(7):1709–1716. doi:10.1038/npp.2015.17
    1. Moieni M, Muscatell KA, Jevtic I, Breen EC, Irwin MR, Eisenberger NI. Sex Differences in the Effect of Inflammation on Subjective Social Status: A Randomized Controlled Trial of Endotoxin in Healthy Young Adults. Front Psychol. 2019;10:2167. Published 2019 Oct 1. doi:10.3389/fpsyg.2019.02167
    1. Muscatell KA, Moieni M, Inagaki TK, et al. Exposure to an inflammatory challenge enhances neural sensitivity to negative and positive social feedback. Brain Behav Immun. 2016;57:21–29. doi:10.1016/j.bbi.2016.03.022
    1. Muscatell KA. Social psychoneuroimmunology: Understanding bidirectional links between social experiences and the immune system. Brain Behav Immun. 2021;93:1–3. doi:10.1016/j.bbi.2020.12.023
    1. O’Connor MF, Bower JE, Cho HJ, et al. To assess, to control, to exclude: effects of biobehavioral factors on circulating inflammatory markers. Brain Behav Immun. 2009;23(7):887–897. doi:10.1016/j.bbi.2009.04.005
    1. Radin AS, Kuhlman KR, Boyle CC, Haydon MD, Bower JE. Using the influenza vaccine as a mild, exogenous inflammatory challenge: When does inflammation peak? Brain Behav Immun Health, 2021;13, 100239.
    1. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24–31. doi:10.1016/j.it.2005.11.006
    1. Scheele D, Striepens N, Güntürkün O, et al. Oxytocin modulates social distance between males and females. J Neurosci. 2012;32(46):16074–16079. doi:10.1523/JNEUROSCI.2755-12.2012
    1. Segerstrom SC, Hardy JK, Evans DR, Greenberg RN. Vulnerability, distress, and immune response to vaccination in older adults. Brain Behav Immun. 2012;26(5):747–753. doi:10.1016/j.bbi.2011.10.009
    1. Sorjoonen K, Falkstedt D, Melin B, Ingre M. The peril of adjusting for baseline when using change as a predictor. doi:10.31234/osf.ioo/6p5hj.
    1. Strike PC, Wardle J, Steptoe A. Mild acute inflammatory stimulation induces transient negative mood. J Psychosom Res. 2004;57(2):189–194. doi:10.1016/S0022-3999(03)00569-5
    1. Tsai MY, Hanson NQ, Straka RJ, et al. Effect of influenza vaccine on markers of inflammation and lipid profile. J Lab Clin Med. 2005;145(6):323–327. doi:10.1016/j.lab.2005.03.009
    1. Willette AA, Lubach GR, Coe CL. Environmental context differentially affects behavioral, leukocyte, cortisol, and interleukin-6 responses to low doses of endotoxin in the rhesus monkey. Brain Behav Immun. 2007;21(6):807–815. doi:10.1016/j.bbi.2007.01.007
    1. Yee JR, Prendergast BJ. Sex-specific social regulation of inflammatory responses and sickness behaviors. Brain Behav Immun. 2010;24(6):942–951. doi:10.1016/j.bbi.2010.03.006
    1. Yirmiya R, Avitsur R, Donchin O, Cohen E. Interleukin-1 inhibits sexual behavior in female but not in male rats. Brain Behav Immun. 1995;9(3):220–233. doi:10.1006/brbi.1995.1021
    1. Yirmiya R. Endotoxin produces a depressive-like episode in rats. Brain Res. 1996;711(1–2):163–174. doi:10.1016/0006-8993(95)01415-2

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir