Inhibition and prevention of monosodium urate monohydrate crystal-induced acute inflammation in vivo by transforming growth factor beta1

Arthritis Rheum. 1996 Jul;39(7):1192-8. doi: 10.1002/art.1780390718.


Objective: We investigated the effects of transforming growth factor beta 1 (TGF beta 1) 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 TGF beta 1 (rHuTGF beta 1; 10-100 pg/animal) and ultrapure TGF beta 1 (UPTGF beta 1; 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 rHuTGF beta 1 preincubated with a specific anti-TGF beta antibody, and the effects of coinjection of crystals and rHuTGF beta 1, were also studied.

Results: UPTGF beta 1 and rHuTGF beta 1 markedly reduced MSU crystal-induced inflammation. Recombinant human TGF beta 1 also reduced inflammation when administered concomitantly with MSU crystals. Moreover, rHuTGF beta 1 and UPTGF beta 1, injected 1 hour after MSU crystal injection, reduced the inflammatory response in a dose-dependent manner. Injection of rHuTGF beta 1 (100 pg/animal) resulted in a > 90% reduction in the maximal white blood cell count, achieved 6 hours after crystal injection. Preincubation of rHuTGF beta 1 with a specific anti-TGF beta 1 antibody significantly (P < 0.01) reversed the inhibitory effect of rHuTGF beta 1 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 rHuTGF beta 1 6 hours after MSU crystal injection.

Conclusion: Exogenous TGF beta 1 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Antibodies, Anti-Idiotypic / administration & dosage
  • Antibodies, Anti-Idiotypic / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gout / chemically induced
  • Gout / prevention & control*
  • Humans
  • Injections, Subcutaneous
  • Leukocyte Count / drug effects
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Time Factors
  • Transforming Growth Factor beta / administration & dosage*
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / pharmacology
  • Uric Acid


  • Antibodies, Anti-Idiotypic
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Uric Acid