Cytokine-induced fever in obese ( fa/ fa) and lean ( Fa/ Fa) Zucker rats.

In earlier work, we reported that genetically obese ( fa/ fa) Zucker rats exhibited significantly greater anorexia than did lean ( Fa/ Fa) Zucker rats to intracerebroventricular infusion of interleukin (IL)-1β. Here, we investigated the fever response of obese ( fa/ fa) and lean ( Fa/ Fa) Zucker rats to intracerebroventricular microinfusion of IL-1β as well as to the following other cytokines: IL-2, IL-6, and tumor necrosis factor-α (TNF-α). Core body temperature was monitored by a radiotelemetry system in freely moving rats. The results show that 1) both IL-1β and IL-6 induce fevers in obese and lean rats; 2) IL-1β induces a significantly higher fever response in obese rats than it does in lean rats; 3) IL-6 induces a significantly higher fever response in lean rats than it does in obese rats; 4) IL-2 induces a moderate fever response in lean but not obese rats; 5) TNF-α induces a similar fever response in obese and lean rats; and 6) the fevers induced by each effective cytokine have different time courses. Thus obese ( fa/ fa) and lean ( Fa/ Fa) Zucker rats show differential responsiveness to the intracerebroventricular microinfusion of various classes of cytokines. This suggests that genetic obesity in the fa/fa Zucker rat is associated with differential cytokine action on thermoregulatory mechanisms.