Production of interleukin-1 receptor antagonist, inflammatory chemotactic proteins, and prostaglandin E by rheumatoid and osteoarthritic synoviocytes--regulation by IFN-gamma and IL-4.
This study analyzes the effects of the T cell cytokines IL-4 and IFN-gamma on the spontaneous and stimulated production of IL-8, MCP-1, IL-1 receptor antagonist (IL-1ra), and PGE by synoviocytes from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Cells from both sources constitutively released IL-8 and MCP-1, but no IL-1ra or PGE. Stimulation with IL-1 beta or TNF-alpha massively increased chemokine production and induced the generation of PGE and low amounts of IL-1ra. The constitutive or cytokine-stimulated release of IL-8 was inhibited by IFN-gamma, but not by IL-4. The constitutive or IL-1 beta-stimulated release of MCP-1, by contrast, was markedly enhanced by IL-4 and IFN-gamma. Both cytokines, however, had only borderline effects on the release stimulated by TNF-alpha. The yield of IL-1ra was strongly enhanced by IFN-gamma in all cases, whereas the effect of IL-4 was pronounced only in IL-1 beta-stimulated OA synoviocytes. IL-4, on the other hand, markedly decreased the release of PGE, which was less susceptible to IFN-gamma. The observed effects on chemokines, IL-1ra expression, and PGE release by synoviocytes suggest that IFN-gamma and IL-4 are important regulatory elements in the inflamed synovium and may exert anti-inflammatory effects.
Seitz
M
M
Division of Rheumatology, University Hospital, Inselspital, Bern, Switzerland.
Loetscher
P
P
Dewald
B
B
Towbin
H
H
Ceska
M
M
Baggiolini
M
M
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D011458:Prostaglandins E; D012795:Sialoglycoproteins; D015847:Interleukin-4; D007371:Interferon-gamma