Inhibition and prevention of monosodium urate monohydrate crystal–induced acute inflammation in vivo by transforming growth factor β1

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Abstract
Objective. We investigated the effects of transforming growth factor β1 (TGFβ1) on monosodium urate monohydrate (MSU) crystal-induced acute inflammation in vivo. Methods. One hour after MSU crystal–induced acute inflammation was produced in the rat subcutaneous air pouch model, the effects of recombinant human TGFβ1 (rHuTGFβ1; 10–100 pg/animal) and ultrapure TGFβ1 (UPTGFβ1; 100 and 500 pg/animal) were assessed, based on absolute and differential white blood cell counts in the exudate. The effects of 10 pg of rHuTGFβ1 preincubated with a specific anti-TGFβ antibody, and the effects of coinjection of crystals and rHuTGFβ1, were also studied. Results. UPTGFβ1 and rHuTGFβ1 markedly reduced MSU crystal–induced inflammation. Recombinant human TGFβ1 also reduced inflammation when administered concomitantly with MSU crystals. Moreover, rHuTGFβ1 and UPTGFβ1, injected 1 hour after MSU crystal injection, reduced the inflammatory response in a dose-dependent manner. Injection of rHuTGFβ1 (100 pg/animal) resulted in a >90% reduction in the maximal white blood cell count, achieved 6 hours after crystal injection. Preincubation of rHuTGFβ1 with a specific anti-TGFβ1 antibody significantly (P < 0.01) reversed the inhibitory effect of rHuTGFβ1 on the inflammatory response. Consistent with the regulation of inflammatory cell recruitment into the joint, the percentage of monocytes markedly decreased (P < 0.01) following local injection with rHuTGFβ1 6 hours after MSU crystal injection. Conclusion. Exogenous TGFβ1 prevents and inhibits MSU crystal–induced acute inflammation in vivo. Its role in the self-limitation of gouty attacks deserves consideration, among the various other factors involved.

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