Differential effects of interleukins 10 and 4 on the production of interleukin-6 by blood and synovium monocytes in rheumatoid arthritis.
OBJECTIVE
To determine how the antiinflammatory cytokines interleukin-10 (IL-10) and IL-4 affect the production of IL-6 in rheumatoid arthritis (RA) and to assess the contribution of IL-10 production.


METHODS
IL-6 production was measured by enzyme-linked immunosorbent assay (ELISA) in the supernatants of cultured RA synovium pieces (from 23 patients), purified RA synovial tissue monocyte/macrophages, and RA blood monocytes, in the presence of IL-10 and IL-4. IL-10 was also detected by ELISA in culture supernatants and in RA sera.


RESULTS
The production of IL-6 by RA synovium was strongly inhibited by IL-4 (46.6%; P = 0.0001) and was inhibited to a lower extent by IL-10 (25.3%; P = 0.03). Likewise, the spontaneous production of IL-6 by RA synovial tissue monocyte/macrophages was decreased by the addition of IL-4 (48.8%) and IL-10 (23.7%). This inhibition of IL-6 production was significantly lower (P < 0.03) than that observed with RA blood monocytes (83.0% for IL-10 and 85.2% for IL-4). Interestingly, and in contrast to RA blood monocytes, RA synovial tissue monocyte/macrophages produced spontaneously high levels of IL-10, which were inhibited by IL-4 and interferon-gamma.


CONCLUSIONS
The ability of IL-10 and IL-4 to suppress IL-6 production was dependent on 1) differences in the state of differentiation of blood and synovial tissue monocytes, and 2) local production of cytokine inside the synovium.
Chomarat
P
P
Schering-Plough Laboratory for Immunological Research, Dardilly, France.
Banchereau
J
J
Miossec
P
P
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology
D015850:Interleukin-6; D016753:Interleukin-10; D015847:Interleukin-4