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

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Abstract
A complete understanding of the role for endogenously produced interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and IL-1 receptor antagonist (IL-1ra) in the acute phase response to inflammation remains unknown. In the present studies, knockout mice lacking either a functional IL-1 type I receptor (IL-1RI−/−), a TNF type I receptor (TNFR-I−/−), or both IL-1 type I and TNF type I receptors (IL-1RI−/−/TNFR-I−/−) received a turpentine abscess. Additional mice deficient in IL-1ra protein (IL-1ra−/−) or overexpressing IL-1ra protein (IL-1ratg) 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. Mice 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 turpentine 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 central role in mitigating the magnitude of the IL-1-mediated inflammatory response and, ultimately, the outcome to a turpentine abscess.

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