Upregulated expression of IL-4 receptors and increased levels of IL-4 in rheumatoid arthritis patients.
The level of IL-4R expression on peripheral lymphocyte subsets from rheumatoid arthritis (RA) patients and controls was studied by flow cytometric analysis of the binding of phycoerythrin-labelled IL-4 (PE-IL-4). In normal lymphocytes, IL-4R is mainly expressed on CD19+ cells, although it was also seen, at lower levels, on CD3+, CD4+ and CD8+ cells. In RA patients, a significantly increased spontaneous expression of IL-4R was observed, compared with controls, in the CD3+, CD4+ and CD19+ cell subsets. No significant differences in IL-4R expression were found between patients receiving steroids and those who were not, suggesting that steroids are not involved in upregulating IL-4R levels in vivo. Because IL-4 is a potent upregulator of IL-4R, we considered the possibility that incremented levels of circulating IL-4 in RA accounted for the high surface expression of IL-4R. By ELISA, we found abnormally high levels of immunoreactive IL-4 in 35.13% of patient serum samples, while it was undetectable in control sera. In addition, we examined IL-4 mRNA expression by polymerase chain reaction (PCR) in the PBMC of patients and controls. IL-4 PCR products were observed in four out of 10 patients studied but in none of the controls. No correlation was observed between the seric concentrations of IL-4 and IL-4R, indicating that activator factors other than IL-4 contribute to the upregulation of IL-4R expression in RA. Since the patients' sedimentation rate and CRP values did not correlate with the concentration of circulating IL-4, we conclude that this lymphokine does not contribute to the deleterious effect of the disease. Rather, due to its antiinflammatory properties, the overproduction of IL-4 in RA may be a compensatory mechanism neutralizing the harmful effect of activated macrophages.
D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis* / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000187:drug effects; D019948:Receptors, Interleukin-4; D015854:Up-Regulation / Q000276:immunology*
D015703:Antigens, CD; D005938:Glucocorticoids; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4