title: Interleukin 4, but not interleukin 10, regulates the production of inflammation mediators by rheumatoid synoviocytes.
abstract: Rheumatoid synovitis is characterized by increased activation and proliferation of synoviocytes, which are an important source of cytokines. The role of Interleukin 4 (IL-4) and IL-10 on the production of mediators of inflammation by rheumatoid synoviocytes was studied herein. While IL-4 weakly affected the spontaneous PGE2 production, it strongly inhibited its production when cells were stimulated with IL-1 beta and TNF-alpha. IL-4 decreased by 60% to 80% the spontaneous and the IL-1 beta or TNF-alpha induced synthesis of GM-CSF. In contrast, IL-4 enhanced the spontaneous (2.6-fold), and to a lower extent (1.3-1.8-fold), the cytokine stimulated production of IL-6. This induction was not due to a passive release of pre-synthesized IL-6, since IL-4 increased the level of IL-6 mRNA expression induced by IL-1 beta. The D50 was 5 U/ml of IL-4 for both the stimulation of IL-6 synthesis and the inhibition of GM-CSF production. Kinetic studies of the action of IL-4 revealed a rapid and sustained inhibition of GM-CSF production, and a late increase of IL-6 secretion. By contrast, IL-10 had no effect on the production of either IL-6 or GM-CSF by synoviocytes. Thus, by inhibiting synoviocyte proliferation and inhibiting their secretion of PGE2 and GM-CSF, IL-4 displays on synoviocytes a series of biological effects which complements its anti-inflammatory properties on monocytes.
authors.affiliation: Schering-Plough Laboratory for Immunological Research, Dardilly, France.
authors.forename: J
authors.initials: J
authors.lastname: Dechanet
authors.forename: M C
authors.initials: MC
authors.lastname: Rissoan
authors.forename: J
authors.initials: J
authors.lastname: Banchereau
authors.forename: P
authors.initials: P
authors.lastname: Miossec
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000503:physiopathology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000276:immunology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015232:Dinoprostone