ALTERED ENERGY-BALANCE AND CYTOKINE GENE-EXPRESSION IN A MURINE MODELOF CHRONIC INFECTION WITH TOXOPLASMA-GONDII

The temporal pattern of changes in energy balance and cytokine mRNA ex pression in spleen and brain were examined in a mouse model of infecti on with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-al pha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hyperm etabolic state persisted during subsequent anorexia, whose onset coinc ided with elevated IL-2, and at the end of the acute phase of cachexia , the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL- 10, and IFN-gamma. In the chronic phase of the infection, the mice sho wed either partial weight recovery (gainers) or no weight regain (nong ainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, excep t for TNF-alpha and IL-10. In contrast, the infected nongainers contin ued to show both anorexia and hypermetabolism, which were associated w ith elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies r eveal a distinct pattern of cytokine mRNA expression underlying I) hyp ermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stabl e weight loss vs. partial weight recovery.