Sex differences in photoperiodic and stress-induced enhancement of immune function in Siberian hamsters Staci D. Bilbo a, * and Randy J. Nelson b a Department of Psychological and Brain Sciences, The Johns Hopkins University, Baltimore, MD 21218, USA b Departments of Psychology and Neuroscience, The Ohio State University, Columbus, OH 43210, USA Received 27 December 2002; received in revised form 2 March 2003; accepted 13 March 2003 Abstract Siberian hamsters breed during the long days of spring and summer when environmental conditions (e.g., ambient temperatures, food availability) are favorable for reproduction. Environmental conditions may also influence the onset and severity of infection and disease, and photoperiodic alterations in immune function may comprise part of a rep- ertoire of seasonal adaptations to help survive winter. In order to test the hypothesis that animals use day length to anticipate seasonal stressors and adjust immune function, we measured antigen-specific delayed-type-hypersensitivity (DTH) responses in the skin of male and female hamsters during long, ‘‘summer-like,’’ or short, ‘‘winter-like’’ days, at baseline and following acute restraint stress. Sex steroid hormones were lower, and cortisol was higher, in males and females during short days. Baseline DTH was enhanced in short- compared to long-day males, and acute stress aug- mented this effect. In contrast, photoperiod alone did not influence the DTH response in females. As predicted, female hamsters exhibited significantly higher DTH responses than males during long days, but not during short days. However, this enhancement was observed in acutely stressed females only. Cortisol concentrations were significantly higher at baseline in females, and increased more in response to stress, compared to males in both photoperiods. These results suggest that photoperiod provides a useful cue by which stressors in the environment may be anticipated in order to adjust immune function. Furthermore, interactions among reproductive status and stress responses appear to mediate the expression of sex differences in immune responses in hamsters. Ó 2003 Elsevier Science (USA). All rights reserved. 1. Introduction Environmental conditions, such as temperature, and the availability of food, water, and shelter, often vary on a seasonal basis. These conditions may influence the onset and severity of infection and disease; for instance, challenging conditions during winter may weaken im- mune function and compromise survival via hypother- mia, starvation, or shock (Afoke et al., 1993; Lack, 1954; Ross et al., 1989). High thermoregulatory demands for small mammals, in particular, during the relatively cold winter months typically coincide with low food avail- ability. The energetic bottleneck faced by animals during winter has led to the evolution of specific adaptations that allow these animals to conserve energy and cope with winter successfully (Heideman and Bronson, 1990; Nelson et al., 1998). One of these adaptations involves the cessation of reproduction; Siberian hamsters (Phodopus sungorus) stop breeding during the winter by responding to day length (photoperiod) cues that allow individuals to anticipate challenging conditions, and prepare accordingly for them (Bartness et al., 1993). Brain, Behavior, and Immunity 17 (2003) 462–472 BRAIN, BEHAVIOR, and IMMUNITY www.elsevier.com/locate/ybrbi * Corresponding author. Fax: 1-614-451-3116. E-mail address: bilbo.1@osu.edu (S.D. Bilbo). 0889-1591/$ - see front matter Ó 2003 Elsevier Science (USA). All rights reserved. doi:10.1016/S0889-1591(03)00063-1