IMPORTANCE OF BRAIN IL-1 TYPE-II RECEPTORS IN FEVER AND THERMOGENESIS IN THE RAT

Interleukin-1 (IL-1) acts centrally to induce fever and thermogenesis in rodents. The central actions of IL-1alpha and IL-1beta apparently involve different mechanisms, and the effects of IL-1beta are not consistent with interaction with a type I (IL-1R(I)) 80-kDa receptor. In the present study the involvement of the type II IL-1 receptor (IL-1R(II)) was tested in the rat by examining the effects of central injection of a monoclonal antibody (ALVA-42), which blocks the IL-1R(II). Pretreatment of rats with ALVA-42 (6 mug icv) inhibited the thermogenic and pyrogenic responses to intracerebroventricular injection of 5 ng (but not 50 ng) of IL-1beta in conscious rats but did not significantly modify responses to IL-1alpha. ALVA-42 also failed to modify the responses to peripherally administered IL-1beta (1 mug) but significantly attenuated the pyrogenic and thermogenic responses to peripheral (125 mug) or central (1 mug) injection of endotoxin. These data indicate that IL-1R(II) mediates the central effects of a low dose of IL-1beta, but not IL-1alpha, on fever and thermogenesis in the rat. They also imply that responses to endotoxin are due, at least in part, to the activation of IL-1R(II) by IL-1beta released within the brain and that effects of peripherally injected IL-1beta involve different mechanisms, probably associated with IL-1R(I).