Altered Acute Phase Responses to Inflammation in IL‐1 and TNF Receptor Knockout Mice a

The acute phase response (APR) to inflammation is characterized by symptoms of fever, lethargy, loss of appetite, and a decrease in food intake. These symptoms are widely recognized in many species of animals and are thought to be regulated responses that facilitate survival.' The cytokines interleukin1 (IL-1) and tumor necrosis factor-a (TNF-a) have been implicated as key mediators in the host defense response to inflammation. Although IL-1 is widely recognized as an endogenous pyrogen (EP), TNF-a has been implicated as both an EP and an endogenous cryogen (EC) or antipyretic2 In order for IL-1 and TNF-a! to induce an effect upon a cell, they must bind to one of their cell surface receptors and activate an intracellular signaling cascade. Two classes of IL-1 receptors have been cloned and are classified as the type I and type I1 receptors. Although both cellular receptors can bind both forms of IL-1 (a! and @), it is the type I receptor that is thought to be solely responsible for the intracellular signaling subsequent to binding.3 The type I1 receptor is thought to be a negative regulator (decoy) of IL-1 function^.^ More recently, the existence of a type I11 IL-1 receptor has been reported by E. B. DeSouza with homology to the type I receptor and the presence of an intracellular domain. The two TNF cloned receptors are termed the p55 (type I) receptor and the p75 (type 11) receptor. Both TNF receptors bind TNF-or and TNF-/3 (lymphotoxin) with similar affinity, but activate different intracellular signaling pathway^.^ TNF-a has been demonstrated to interact with both the type I and type I1 receptors, with