Transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals.
Systemic administration of the cytokine, TGF beta 1, profoundly antagonized the development of polyarthritis in susceptible rats. TGF beta 1 administration (1 or 5 micrograms/animal), initiated one day before an arthritogenic dose of streptococcal cell wall (SCW) fragments, virtually eliminated the joint swelling and distortion typically observed during both the acute phase (articular index, AI = 2.5 vs. 11; P less than 0.025) and the chronic phase (AI = 0 vs. 12.5) of the disease. Moreover, TGF beta 1 suppressed the evolution of arthritis even when administration was begun after the acute phase of the disease. Histopathological examination of the joint revealed the systemic TGF beta 1 treatment greatly reduced inflammatory cell infiltration, pannus formation, and joint erosion. Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF beta 1 reversed the leukocytosis associated with the chronic phase of the arthritis. Control animals subjected to the same TGF beta 1 dosing regimen displayed no discernable immunosuppressive or toxic effects even after 4 wk of treatment. These observations not only provide insight into the immunoregulatory effects of TGF beta, but also implicate this cytokine as a potentially important therapeutic agent.
Brandes
M E
ME
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Allen
J B
JB
Ogawa
Y
Y
Wahl
S M
SM
D000208:Acute Disease; D000818:Animals; D001168:Arthritis / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D002473:Cell Wall / Q000276:immunology; D002908:Chronic Disease; D007958:Leukocyte Count / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013291:Streptococcus / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000009:adverse effects / Q000627:therapeutic use*
D016212:Transforming Growth Factor beta