Suppression of bacterial cell wall-induced polyarthritis by recombinant gamma interferon.
Group A streptococcal cell wall fragments (SCW) induce erosive polyarthritis, characterized by synovial cell hyperplasia and intense mononuclear cell infiltration, in susceptible rats. Because of the known antiproliferative and immunomodulatory effects of interferon (IFN), we evaluated the effect of systemically administered alpha, beta and gamma IFN on the evolution of these destructive lesions. Treatment with gamma IFN not only reduced the acute response, but had an even greater suppressive effect on the chronic mononuclear cell-mediated destructive phase of the disease (articular index 10.2 +/- 1.2 for SCW only versus 3.8 +/- 0.7 for SCW + gamma IFN; p less than 0.01). Treatment with gamma IFN was more effective in the suppression of the arthritis than alpha, beta IFN. Histopathologic evaluation of the joints demonstrated that gamma IFN-treated animals had significantly fewer inflammatory cells, and less synovial hyperplasia and erosions than the SCW controls. gamma IFN suppression of mononuclear cell prostaglandin synthesis and synovial fibroblast proliferation was consistent with its anti-arthritic effects. These data indicate that the pathophysiology of SCW-induced erosive polyarthritis is subject to regulatory control by gamma IFN and that the mechanisms of suppression may be relevant in the treatment of rheumatoid arthritis.
Allen
J B
JB
Cellular Immunology Section, NIDR, NIH, Bethesda, MD 20892.
Bansal
G P
GP
Feldman
G M
GM
Hand
A O
AO
Wahl
L M
LM
Wahl
S M
SM
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001169:Arthritis, Experimental / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D002455:Cell Division / Q000187:drug effects; D002473:Cell Wall; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D015232:Dinoprostone / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D007370:Interferon Type I / Q000627:therapeutic use; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000032:analysis; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011135:Polysaccharides, Bacterial; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D013297:Streptococcus pyogenes; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001095:Arachidonic Acids; D007370:Interferon Type I; D007375:Interleukin-1; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015232:Dinoprostone