Modulation of the acute phase response by altered expression of the IL-1 type 1 receptor or IL-1ra

A complete understanding of the role for endogenously produced interleukin- l (IL-1), tumor necrosis factor-a (TNF-a), and IL-1 receptor antagonist (IL -1ra) in the acute phase response to inflammation remains unknown. In the p resent studies, knockout mice lacking either a functional IL-1 type I recep tor (IL-1RI(-/-)), a TNF type I receptor (TNFR-I-/-), or both IL-1 type I a nd TNF type I receptors (IL-1RI(-/-)/TNFR-I-/-) received a turpentine absce ss. Additional mice deficient in IL-1ra protein (IL-1ra(-/-)) or overexpres sing IL-1ra protein (IL-1ra(tg)) were similarly treated. After a turpentine abscess, IL-1 receptor knockout mice exhibited an attenuated inflammatory response compared with wild-type or animals lacking a functional TNFR-I. Mi ce overexpressing IL-1ra also had an attenuated hepatic acute phase protein response, whereas IL-1ra knockout mice had a significantly greater hepatic acute phase response. We conclude that the inflammatory response to a turp entine abscess is the result of a balance between IL-1ra expression and IL- 1 binding to its type I receptor. Endogenously produced IL-1ra plays a cent ral role in mitigating the magnitude of the IL-l-mediated inflammatory resp onse and, ultimately, the outcome to a turpentine abscess.