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


CONCLUSIONS
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.
Lioté
F
F
Laboratoire d' Histopathologie synoviale (ER254), Université Paris VII, Paris, France.
Prudhommeaux
F
F
Schiltz
C
C
Champy
R
R
Herbelin
A
A
Ortiz-Bravo
E
E
Bardin
T
T
D000208:Acute Disease; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006073:Gout / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D007279:Injections, Subcutaneous; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D014527:Uric Acid
D000888:Antibodies, Anti-Idiotypic; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014527:Uric Acid