Background/Aim: Sickness behaviors are the behavioral alterations animals exhibit during the course of an infection, often accompanied by reduced reproductive activity. Adopting sickness behaviors may aid in overcoming the infection, by diverting energy from routine activities towards enhancement of the immune system. Nonetheless, sickness behaviors are plastic, being influenced by specific environmental and social circumstances. Here, we tested whether the presentation of a novel female to males suffering from a simulated infection could impact the behavioral effects of sickness, the reproductive axis, or both. Methods: Male zebra finches were housed in isolation and injected intramuscularly with lipopolysaccharide or saline. Behaviors were recorded before (3 h before injection) and after (3.5 h after injection) addition of a novel female to the cage for 30 min. Four hours after injection, we collected the brain and testis for the analysis of important reproductive axis modulators, gonadotropin-releasing hormone, and gonadotropin-inhibitory hormone, and to quantify gene expression of a proinflammatory cytokine involved in the regulation of sickness behaviors [interleukin (IL)-1β]. Testosterone was quantified in the plasma. Results: The presence of a novel female diminished sickness behaviors and induced alterations in the reproductive axis within 30 min, with no associated changes in brain gene expression of IL-1β. Social environment itself altered brain gene expression of IL-1β. Conclusions: Male zebra finches prioritize the opportunity to mate versus investment in recovery from an infection, as determined by reduced expression of sickness behaviors when a potential mate was present. The behavioral effects of IL-1β appear to be context dependent in this species.

Hart B: Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 1988;12:123-137.
Layé S, Gheusi G, Cremona S, et al: Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression. Am J Physiol Regul Integr Comp Physiol 2000;279:R93-R98.
Dantzer R: Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity. Eur J Pharmacol 2004;500:399-411.
Quan N, Whiteside M, Herkenham M: Time course and localization patterns of interleukin-1β messenger RNA expression in brain and pituitary after peripheral administration of lipopolysaccharide. Neuroscience 1998;83:281-293.
Ek M, Kurosawa M, Lundeberg T: Activation of vagal afferents after intravenous injection of interleukin-1β: role of endogenous prostaglandins. J Neurosci 1998;18:9471-9479.
Goehler LE, Gaykema R, Nguyen KT: Interleukin-1β in immune cells of the abdominal vagus nerve: a link between the immune and nervous systems? J Neurosci 1999;19:2799-2806.
Harris TG, Battaglia DF, Brown ME, Brown MB, Carlson NE, Viguié C, Williams CY, Karsch FJ: Prostaglandins mediate the endotoxin-induced suppression of pulsatile gonadotropin-releasing hormone and luteinizing hormone secretion in the ewe. Endocrinology 2000;141:1050-1058.
Rivier C, Vale W: Cytokines act within the brain to inhibit luteinizing hormone secretion and ovulation in the rat. Endocrinology 1990;127:849-856.
Ebisui O, Fukata J, Tominaga T, Murakami N, Kobayashi H, Segawa H, Muro S, Naito Y, Nakai Y, Masui Y, Nishida T, Imura H: Roles of interleukin-1 alpha and -1 beta in endotoxin-induced suppression of plasma gonadotropin levels in rats. Endocrinology 1992;130:3307-3313.
He D, Sato I, Kimura F, Akema T: Lipopolysaccharide inhibits luteinizing hormone release through interaction with opioid and excitatory amino acid inputs to gonadotropin-releasing hormone neurones in female rats: possible evidence for a common mechanism involved in infection and immobilization stress. J Neuroendocrinol 2003;15:559-563.
Iwasa T, Matsuzaki T, Murakami M, Shimizu F, Kuwahara A, Yasui T, Irahara M: Decreased expression of kisspeptin mediates acute immune/inflammatory stress-induced suppression of gonadotropin secretion in female rat. J Endocrinol Invest 2008;31:656-659.
Rivest S, Rivier C: Centrally injected interleukin-1-beta inhibits the hypothalamic LHRH secretion and circulating LH levels via prostaglandins in rats. J Neuroendocrinol 1993;5:445-450.
Watanobe H, Hayakawa Y: Hypothalamic interleukin-1β and tumor necrosis factor-α, but not interleukin-6, mediate the endotoxin-induced suppression of the reproductive axis in rats. Endocrinology 2003;144:4868-4875.
Xiao E, Xia-Zhang L, Ferin M: Inhibitory effects of endotoxin on LH secretion in the ovariectomized monkey are prevented by naloxone but not by an interleukin-1 receptor antagonist. Neuroimmunomodulation 1999;7:6-15.
Williams CY, Harris TG, Battaglia DF, Viguié C, Karsch FJ: Endotoxin inhibits pituitary responsiveness to gonadotropin-releasing hormone. Endocrinology 2001;142:1915-1922.
Turnbull AV, Rivier C: Inhibition of gonadotropin-induced testosterone secretion by the intracerebroventricular injection of interleukin-1 beta in the male rat. Endocrinology 1997;138:1008-1013.
Owen-Ashley NT, Turner M, Hahn TP, Wingfield JC: Hormonal, behavioral, and thermoregulatory responses to bacterial lipopolysaccharide in captive and free-living white-crowned sparrows (Zonotrichia leucophrys gambelii). Horm Behav 2006;49:15-29.
Adelman JS, Bentley GE, Wingfield JC, Martin LB, Hau M: Population differences in fever and sickness behaviors in a wild passerine: a role for cytokines. J Exp Biol 2010;213:4099-4109.
Lopes PC, Wingfield JC, Bentley GE: Lipopolysaccharide injection induces rapid decrease of hypothalamic GnRH mRNA and peptide, but does not affect GnIH in zebra finches. Horm Behav 2012;62:173-179.
Kent S, Bluthé RM, Dantzer R, Hardwick AJ, Kelley KW, Rothwell NJ, Vannice JL: Different receptor mechanisms mediate the pyrogenic and behavioral-effects of interleukin-1. Proc Natl Acad Sci USA 1992;89:9117-9120.
Miller NE: Some psychophysiological studies of motivation and of the behavioral-effects of illness. Bull Br Psychol Soc 1964;17:1-20.
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;11:107-118.
Yirmiya R, Avitsur R, Donchin O, Cohen E: Interleukin-1 inhibits sexual behavior in female but not in male rats. Brain Behav Immun 1995;9:220-233.
Weil ZM, Bowers SL, Pyter LM, Nelson RJ: Social interactions alter proinflammatory cytokine gene expression and behavior following endotoxin administration. Brain Behav Immun 2006;20:72-79.
Yee JR, Prendergast BJ: Sex-specific social regulation of inflammatory responses and sickness behaviors. Brain Behav Immun 2010;24:942-951.
Lopes PC, Adelman J, Wingfield JC, Bentley GE: Social context modulates sickness behavior. Behav Ecol Sociobiol 2012;66:1421-1428.
Alexander J, Stimson WH: Sex-hormones and the course of parasitic infection. Parasitol Today 1988;4:189-193.
Grossman CJ: Interactions between the gonadal steroids and the immune system. Science 1985;227:257-261.
Nelson RJ, Demas GE: Seasonal changes in immune function. Q Rev Biol 1996;71:511-548.
Schuurs A, Verheul H: Effects of gender and sex steroids on the immune response. J Steroid Biochem Mol Biol 1990;35:157-172.
Casto JM, Nolan V, Ketterson ED: Steroid hormones and immune function: experimental studies in wild and captive dark-eyed juncos (Junco hyemalis). Am Nat 2001;157:408-420.
Deviche P, Cortez L: Androgen control of immunocompetence in the male house finch, Carpodacus mexicanus Müller. J Exp Biol 2005;208:1287-1295.
Duffy DL, Bentley GE, Drazen DL, Ball GF: Effects of testosterone on cell-mediated and humoral immunity in non-breeding adult European starlings. Behav Ecol 2000;11:654-662.
Evans MR, Goldsmith AR, Norris S: The effects of testosterone on antibody production and plumage coloration in male house sparrows (Passer domesticus). Behav Ecol Sociobiol 2000;47:156-163.
Owen-Ashley NT, Hasselquist D, Wingfield JC: Androgens and the immunocompetence handicap hypothesis: unraveling direct and indirect pathways of immunosuppression in song sparrows. Am Nat 2004;164:490-505.
Peters A: Testosterone treatment is immunosuppressive in superb fairy-wrens, yet free-living males with high testosterone are more immunocompetent. Proc Biol Sci 2000;267:883-889.
Ansar Ahmed AS, Dauphinee MJ, Talal N: Effects of short-term administration of sex hormones on normal and autoimmune mice. J Immunol 1985;134:204-210.
Bilbo SD, Nelson RJ: Sex steroid hormones enhance immune function in male and female Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 2001;280:R207-R213.
Olsen NJ, Kovacs WJ: Gonadal steroids and immunity. Endocr Rev 1996;17:369-384.
Hasselquist D, Marsh JA, Sherman PW: Is avian humoral immunocompetence suppressed by testosterone? Behav Ecol Sociobiol 1999;45:167-175.
Roberts ML, Buchanan KL, Hasselquist D, Evans MR: Effects of testosterone and corticosterone on immunocompetence in the zebra finch. Horm Behav 2007;51:126-134.
Ros A, Groothuis T, Apanius V: The relation among gonadal steroids, immunocompetence, body mass, and behavior in young black-headed gulls (Larus ridibundus). Am Nat 1997;150:201-219.
Wingfield JC, Lynn SE, Soma KK: Avoiding the ‘costs' of testosterone: ecological bases of hormone-behavior interactions. Brain Behav Evol 2001;57:239-251.
Oliveira RF: Social modulation of androgens in vertebrates: mechanisms and function. Adv Stud Behav 2004;34:165-239.
Li ZG, Danis VA, Brooks PM: Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells in vitro. Clin Exp Rheumatol 1993;11:157-162.
Bellido T, Jilka RL, Boyce BF, Girasole G: Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor. J Clin Invest 1995;95:2886-2895.
D'Agostino P, Milano S, Barbera C, Di Bella G, La Rosa M, Ferlazzo V, Farruggio R, Miceli DM, Miele M, Castagnetta L, Cillari E: Sex hormones modulate inflammatory mediators produced by macrophages. Ann NY Acad Sci 1999;876:426-429.
Hatakeyama H, Nishizawa M, Nakagawa A, Nakano S, Kigoshi T, Uchida K: Testosterone inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells. FEBS Lett 2002;530:129-132.
Ashley NT, Hays QR, Bentley GE, Wingfield JC: Testosterone treatment diminishes sickness behavior in male songbirds. Horm Behav 2009;56:169-176.
Burness G, Armstrong C, Fee T, Tilman-Schindel E: Is there an energetic-based trade-off between thermoregulation and the acute phase response in zebra finches? J Exp Biol 2010;213:1386-1394.
McGuire NL, Bentley GE: Neuropeptides in the gonads: from evolution to pharmacology. Front Pharmacol 2010;1:114.
Zhao S, Fernald RD: Comprehensive algorithm for quantitative real-time polymerase chain reaction. J Comput Biol 2005;12:1047-1064.
Perfito N, Zann R, Ubuka T, Bentley G, Hau M: Potential roles for GNIH and GNRH-II in reproductive axis regulation of an opportunistically breeding songbird. Gen Comp Endocrinol 2001;173:20-26.
Wingfield JC, Hegner RE, Lewis DM: Circulating levels of luteinizing hormone and steroid hormones in relation to social status in the cooperatively breeding white-browed sparrow weaver, Plocepasser mahali. J Zool 1991;225:43-58.
Cohen J: A power primer. Psychol Bull 1992;112:155-159.
Hertelendy F, Lintner F, Asem EK, Raab B: Synergistic effect of gonadotropin releasing hormone on LH-stimulated progesterone production in granulosa cells of the domestic fowl (Gallus domesticus). Gen Comp Endocrinol 1982;48:117-122.
Flickinger GL: Response of the testes to social interaction among grouped chickens. Gen Comp Endocrinol 1966;6:89-98.
Calisi RM, Díaz-Muñoz SL, Wingfield JC, Bentley GE: Social and breeding status are associated with the expression of GnIH. Genes Brain Behav 2011;10:557-564.
Dufty AM, Wingfield JC: The influence of social cues on the reproductive endocrinology of male brown-headed cowbirds: field and laboratory studies. Horm Behav 1986;20:222-234.
Feder HH, Storey A, Goodwin D, Reboulleau C, Silver R: Testosterone and ‘5alpha-dihydrotestosterone' levels in peripheral plasma of male and female ring doves (Streptopelia risoria) during the reproductive cycle. Biol Reprod 1977;16:666-677.
Pinxten R, de Ridder E, Eens M: Female presence affects male behavior and testosterone levels in the European starling (Sturnus vulgaris). Horm Behav 2003;44:103-109.
Runfeldt S, Wingfield JC: Experimentally prolonged sexual activity in female sparrows delays termination of reproductive activity in their untreated mates. Anim Behav 1985;33:403-410.
Spinedi E, Suescun MO, Hadid R, Daneva T, Gaillard RC: Effects of gonadectomy and sex-hormone therapy on the endotoxin-stimulated hypothalamo-pituitary-adrenal axis - evidence for a neuroendocrine-immunological sexual dimorphism. Endocrinology 1992;131:2430-2436.
Prendergast BJ, Baillie SR, Dhabhar FS: Gonadal hormone-dependent and -independent regulation of immune function by photoperiod in Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 2008;294:R384-R392.
Owen-Ashley NT, Wingfield JC: Seasonal modulation of sickness behavior in free-living northwestern song sparrows (Melospiza melodia morphna). J Exp Biol 2006;209:3062-3070.
De Miguel Z, Vegas O, Garmendia L, Arregi A, Beitia G, Azpiroz A: Behavioral coping strategies in response to social stress are associated with distinct neuroendocrine, monoaminergic and immune response profiles in mice. Behav Brain Res 2011;225:554-561.
Meltzer JC, MacNeil BJ, Sanders V, Pylypas S, Jansen AH, Greenberg AH, Nance DM: Stress-induced suppression of in vivo splenic cytokine production in the rat by neural and hormonal mechanisms. Brain Behav Immun 2004;18:262-273.
Stearns SC: The Evolution of Life Histories. Oxford, Oxford University Press, 1992.
Adelman JS, Martin LB: Vertebrate sickness behaviors: adaptive and integrated neuroendocrine immune responses. Integr Comp Biol 2009;49:202-214.
Larson SJ, Romanoff RL, Dunn AJ, Glowa JR: Effects of interleukin-1 beta on food-maintained behavior in the mouse. Brain Behav Immun 2002;16:398-410.
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