Trait-specific effects of exogenous triiodothyronine on cytokine and behavioral responses to simulated systemic infection in male Siberian hamsters

Abstract

Seasonal changes in day length enhance and suppress immune function in a trait-specific manner. In Siberian hamsters (Phodopus sungorus) winter-like short days (SDs) increase blood leukocyte concentrations and adaptive T cell dependent immune responses, but attenuate innate inflammatory responses to simulated infections. Thyroid hormone (TH) signaling also changes seasonally and has been implicated in modulation of the reproductive axis by day length. Immunologically, TH administration in long days (LD) enhances adaptive immune responses in male Siberian hamsters, mimicking effects of SDs. This experiment tested the hypothesis that T3 is also sufficient to mimic the effects of SD on innate immune responses. Adult male hamsters housed in LDs were pretreated with triiodothyronine (T3; 1 μg, s.c.) or saline (VEH) daily for 6 weeks; additional positive controls were housed in SD and received VEH, after which cytokine, behavioral, and physiological responses to simulated bacterial infection (lipopolysaccharide; LPS) were evaluated. SD pretreatment inhibited proinflammatory cytokine mRNA expression (i.e. interleukin 1β, nuclear factor kappa-light-chain-enhancer of activated B cells). In addition, the magnitude and persistence of anorexic and cachectic responses to LPS were also lower in SD hamsters, and LPS-induced inhibition of nest building behavior was absent in SD. T3 treatments failed to affect behavioral (food intake, nest building) or somatic (body mass) responses to LPS in LD hamsters, but one CNS cytokine response to LPS (e.g., hypothalamic TNFα) was augmented by T3. Together these data implicate thyroid hormone signaling in select aspects of innate immune responses to seasonal changes in day length.