Altered mechanisms of fever in aged rats: From periphery to brain
Fever can be induced with lipopolysaccharides (LPS), endotoxins released from Gram-negative bacteria. LPS stimulates the immune system to produce cytokines, some of which (e.g. interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNFα)) are proinflammatory and elicit fever responses. Peripherally induced proinflammatory cytokines ultimately reach the brain and cause the synthesis and release of prostaglandin E2, which initiates behavioral, autonomic and endocrine responses necessary to raise body temperature (Tb). Previously we reported that old rats show blunted fevers compared to young rats when they are maintained at standard room temperatures (21–24°C), but will generate fevers similar to those of young rats when they are either allowed to choose a warmer ambient temperature (Ta) or are housed at a warmer Ta. This dissertation examined age-related differences in two parts of the fever pathway at a standard Ta (21°C) and a warmer Ta (31°C): (1) heat production and heat loss during fever in young and old rats at 21 and 31°C and (2) the passage of the proinflammatory cytokine IL-1β from blood to brain at the two Tas. In brief, we found that in contrast to the other three groups, which all showed good fever responses to LPS, old rats at 21°C showed a decline in metabolic rate and a concomitant lower passage of IL-1β into the brain.