Inhibition of the production of proinflammatory cytokines and immunoglobulins by interleukin-4 in an ex vivo model of rheumatoid synovitis.
OBJECTIVE
To assess the spontaneous production of proinflammatory cytokines and immunoglobulins in rheumatoid arthritis (RA) synovitis and modulation by interleukin-4 (IL-4).


METHODS
We developed an ex vivo model of RA synovitis using pieces of RA synovium, and have studied the regulation of the production of IL-1 beta, IL-6, tumor necrosis factor alpha (TNF alpha), IgM, and IgG.


RESULTS
Spontaneous production of proinflammatory cytokines in vitro was active, with prolonged cytokine gene transcription and translation. IL-6 was produced at higher levels than either IL-1 beta or TNF alpha, and explants produced more IgG than IgM. In contrast, IL-4 and interferon-gamma were undetectable. When pieces of synovium were incubated in the presence of IL-4, reduction of spontaneous proinflammatory cytokine and Ig production was observed.


CONCLUSIONS
These results extend the observations of the antiinflammatory properties of IL-4 to an ex vivo situation, and provide the rationale for the clinical use of IL-4 in RA.
Miossec
P
P
Department of Immunology, Hôpital Edouard Herriot, Lyon, France.
Briolay
J
J
Dechanet
J
J
Wijdenes
J
J
Martinez-Valdez
H
H
Banchereau
J
J
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4