Interleukin 4 inhibits polyclonal immunoglobulin secretion and cytokine production by peripheral blood mononuclear cells from rheumatoid arthritis patients.
Rheumatoid arthritis (RA) is associated with T- and B-cell dysfunction. Immunoglobulin (Ig) production is under the control of T cells and their derived cytokines such as interleukin 2 (IL-2) and IL-4. Herein we studied the regulation of the production of immunoglobulins and cytokines by peripheral blood mononuclear cells from RA patients and controls. In the controls, IL-4 inhibited Ig production in response to Staphylococcus aureus and pokeweed mitogen stimulation. IL-2 induced maximal Ig production in association with Staphylococcus aureus, whereas it inhibited pokeweed mitogen-induced production. In patients, levels of Ig production in response to mitogens and cytokines were reduced, particularly for the response to IL 2. The inhibitory effect of IL-4 on mitogen-induced Ig production was observed in RA patients as in the controls. Spontaneous production of IL-6 was increased in RA patients. These levels were correlated with indicators of active disease such as sedimentation rate and Ritchie index. IL-4 inhibited the production of IL-6, IL-1 beta, and tumor necrosis factor alpha (TNF alpha) by both controls and rheumatoid patients. Thus as first described for the T-cell response, mononuclear cells from RA patients display a reduced response to mitogens and cytokines which induce their B-cell differentiation into Ig-screening cells. However, IL-4 was able to inhibit Ig and cytokine production, properties suggesting a potential antiinflammatory role for this cytokine.
Briolay
J
J
Schering-Plough Laboratory for Immunological Research, Dardilly, France.
Dechanet
J
J
Blanchard
D
D
Banchereau
J
J
Miossec
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007136:Immunoglobulins / Q000096:biosynthesis*; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011043:Pokeweed Mitogens / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011043:Pokeweed Mitogens; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4