Photoperiod, Melatonin, and Sickness Behaviors

描述(由申请人提供)：感染导致迅速出现适应性疾病反应，称为急性期反应，包括发烧、睡眠增加等生理变化，以及食物和水摄入量减少、活动、探索和社会互动等行为变化。这些所谓的“疾病行为”是有组织的适应性策略，通常对宿主的生存至关重要，而不是疾病的非特定表现。建立免疫反应在能量上是昂贵的。对于生活在非热带栖息地的许多动物来说，每年冬天都会出现可预见的年度能源短缺。在冬季的短短的几天里，食物供应不足往往与低温下的高体温调节需求相吻合。在动物中进化出了特定的保存能量的适应方式，如抑制繁殖和生长，以提高冬季的存活率。免疫功能和对感染的反应也受到可用能量的限制，并可能因外部环境的变化而改变。拟议的实验旨在调查疾病行为或免疫细胞运输是否可能受到可用能量或褪黑激素发出信号的其他因素的影响。这项拟议研究的具体目标是：(1)确定早期免疫激活是否会引起长期的生殖成本。(2)确定疾病反应的短日变化是否由褪黑素介导。(3)发现褪黑素是否直接作用于淋巴细胞以改变细胞因子的产生。(4)探讨短日照和褪黑素是否通过影响脑内环氧合酶(COX)和白介素1α(IL-1a)水平而缩短发热持续时间。(5)确定光周期和褪黑素是否影响免疫细胞数量和白细胞的运输。(6)确定光周期是否影响应激对免疫功能的影响程度。综上所述，这些研究可能揭示褪黑素在治疗发烧和厌食症方面的新用途。

DESCRIPTION (provided by applicant): 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.