Melatonin Regulates Energy Balance and Attenuates Fever in Siberian Hamsters

Abstract

Fever is considered an important host defense response but requires significant metabolic energy. During winter many animals must balance immune function with competing physiological demands (i.e. thermoregulation) to survive. Winterlike patterns of melatonin secretion induce a number of energy-saving adaptations. For instance, Siberian hamsters attenuate the duration of fever during simulated short winter day lengths, presumably to conserve energy. To determine the proximate role of melatonin in mediating this photoperiodic response, hamsters housed in long days were injected with saline or melatonin 4 h before lights off for either 1 or 6 wk and assessed for fever following injections of bacterial lipopolysaccharide. Fever duration was attenuated (32%) only in hamsters that decreased body mass, increased cortisol, and exhibited gonadal regression in response to 6 wk of melatonin. Because melatonin-treated hamsters lost significant body mass, fever was assessed in a second long-day group following ad libitum food intake, food restriction, or 24-h food deprivation. Food restriction sufficient to reduce body mass by approximately 25%, but not to reduce leptin, did not influence fever, and 24-h food deprivation virtually abolished fever. Our data suggest that long-term exposure to long-duration melatonin signals is required to induce the physiological changes necessary for short-day immune responses, perhaps involving interactions with hormones such as cortisol and leptin.

Pineal-dependent and -independent effects of photoperiod on immune function in Siberian hamsters (Phodopus sungorus)

“…The protracted febrile responses to LPS observed in LD hamsters appeared to arise largely from the earlier T c decline associated with the onset of the light phase in saline-treated LD hamsters. This suggests that the photoperiodic differences in fever duration between LD and SD reported here and elsewhere (Bilbo and Nelson, 2002;Bilbo et al, 2002b) may be due in part to entrainment of the circadian rhythm in body temperature. Given that the generation of circadian rhythms in the periphery is driven by the neural and humoral output of the SCN (Silver et al, 1996;Meyer-Bernstein et al, 1999;Kramer et al, 2001), and is almost entirely independent of any reciprocal influence by the pineal gland or melatonin (Sumova and Illnerova, 1996;Prendergast and Freeman, 1999), PINx would be expected to have little effect on photoperiodic differences in the febrile response to LPS if such differences are due solely to circadian factors.…”

“…Consequently, little is known about the extent to which photoperiodic changes in immune function rely on the endogenous production of pineal melatonin signals. In one previous experiment, pharmacological injections of melatonin delivered daily 4 h before the onset of darkness (so as to lengthen the endogenous melatonin profile) mimicked the effects of short-days on febrile responses to a simulated infection, suggesting that the duration of melatonin is sufficient in this regard (Bilbo and Nelson, 2002); a similar paradigm yielded comparable results on circulating leukocyte concentrations (Prendergast et al, 2003b). Pineal dependence of innate immunity has been inferred from a study which maintained hamsters in constant light, suppressing endogenous melatonin secretion (Yellon et al, 2005); pineal dependence of adaptive immunity has been inferred from an experiment which exposed pinealectomized hamsters to short days for 1 week prior to antigenic challenge (Yellon et al, 1999b).…”

Winter day lengths enhance T lymphocyte phenotypes, inhibit cytokine responses, and attenuate behavioral symptoms of infection in laboratory rats

“…Pineal melatonin may figure prominently in the transduction of day length information into the immune system of rats, as is the case in hamsters (Wen et al, 2007). Substrates in the immune system and in the CNS that participate in the generation of sickness behaviors may respond directly or indirectly to changes in melatonin secretion (Bilbo & Nelson, 2002;Hotchkiss & Nelson, 2002). In addition, photoperiodic changes in corticosterone secretion may also constitute a post-pineal mechanism relevant to seasonal changes in the immune system.…”

Diurnal and seasonal changes in <i>IL-6</i> and <i>IL-18</i> gene expression in blood leukocytes of male chickens with experimental peritonitis: the impact of lighting conditions and melatonin

“…This phenomenon does not seem to be limited solely to the chicken, because similar results have been obtained in the Siberian hamster (Phodopus sungorus), a seasonal breeder. In this species, a short day length attenuated the symptoms of infection (Bilbo and Nelson, 2002) and compromised both the development of peritoneal inflammation and mitogen-stimulated splenocyte proliferation (Pawlak et al, , 2009.…”