Infection results in the rapid onset of adaptive sickness responses, termed the acute phase response, and includes physiological changes such as fever, increased sleep, as well as behavioral changes such as reduced food and water intake, activity, exploration, and social interactions. These so-called """"""""sickness behaviors"""""""" are organized, adaptive strategies that are often crucial for host survival, rather than nonspecific manifestations of illness. Mounting an immune response is energetically costly. For many animals living in non-tropical habitats, a predictable annual energy shortage occurs each winter. During the short days of winter, low food availability often coincides with high thermoregulatory demands in low temperatures. Specific adaptations to conserve energy, such as inhibiting reproduction and growth, have evolved among animals to enhance winter survival. Immune function and responses to infection are also constrained by available energy, and may be altered by changes in the external environment. The proposed experiments are designed to investigate whether sickness behaviors or immune cell trafficking may be influenced by available energy or other factors signaled by melatonin.
The specific aims of the proposed research are: (1) To determine if early immune activation evokes long-term reproductive costs. (2) To determine if short-day alterations in sickness responses are mediated by melatonin. (3) To discover if melatonin acts directly on lymphocytes to alter cytokine production. (4) To determine if short days and melatonin reduce the duration of fever by affecting brain levels of cyclooxygenase (COX) and interleukin(IL)-1a. (5) To determine if photoperiod and melatonin affect immune cell populations and leukocyte trafficking. (6) To determine if photoperiod influences the extent to which stress compromises immune function. Taken together, these studies may reveal novel therapeutic uses of melatonin on fever and anorexia.
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