Differential in vitro effects of IL-4, IL-10, and IL-13 on proinflammatory cytokine production and fibroblast proliferation in rheumatoid synovium.
The purpose of this study was to compare the potential of interleukin-4 (IL-4), IL-10, and IL-13 to interrupt two major inflammatory pathways in rheumatoid arthritis (RA), i.e., overexpression of proinflammatory cytokines and cytokine-mediated fibroblast growth. IL-4, IL-10, and IL-13 were all able to significantly inhibit the production of IL-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 by freshly isolated RA synovial tissue cells, IL-10 was most effective in terms of IL-1beta and TNF-alpha reduction. The IL-1 receptor antagonist was enhanced by IL-4 and IL-13, but only slightly enhanced by IL-10. Spontaneous interferon-gamma secretion was diminished by IL-4 and IL-10 but not by IL-13. Addition of anti-IL-10 neutralizing antibody to RA synovial tissue cells resulted in a substantial increase in IL-1beta and TNF-alpha levels, whereas neither anti-IL-4 nor anti-IL-13 antibody had a significant effect. IL-1beta-stimulated proliferation of RA synovial fibroblast cell lines was inhibited by IL-4 and IL-13, but not by IL-10; IL-4 was over tenfold more effective than IL-13. These results suggest that IL-4, IL-10, and IL-13 all have the therapeutic potential to regulate the disease activity mediated by proinflammatory cytokines in RA, but each cytokine may have different potencies.
Department of Medicine III, Okayama University Medical School, Japan.
Y
Y
Morita
M
M
Yamamura
M
M
Kawashima
T
T
Aita
S
S
Harada
H
H
Okamoto
H
H
Inoue
H
H
Makino
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D018793:Interleukin-13 / Q000276:immunology / Q000494:pharmacology*; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D007375:Interleukin-1; D018793:Interleukin-13; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4