Interleukin 10 cooperates with interleukin 4 to suppress inflammatory cytokine production by freshly prepared adherent rheumatoid synovial cells
Sugiyama, E.; Kuroda, A.; Taki, H.; Ikemoto, M.; Hori, T.; Yamashita, N.; Maruyama, M.; Kobayashi, M.
Journal of Rheumatology 22(11): 2020-2026
1995
ISSN/ISBN: 0315-162X PMID: 8596138 Document Number: 450112
Objective: Inflammatory cytokines have been implicated as important mediators of inflammation in rheumatoid arthritis (RA). We investigated whether interleukin 4 (IL-4) and interleukin 10 (IL-10) suppress the production of inflammatory cytokines by freshly prepared adherent rheumatoid synovial cells. Methods: Adherent synovial cells were obtained from the rheumatoid synovium by collagenase digestion. The levels of IL-1-beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 in culture supernatants were measured by ELISA. The gene expressions of IL-6 and IL-8 were determined by Northern blot analysis. Results: Freshly prepared rheumatoid synovial cells spontaneously produced large amounts of IL-6 and IL-8. However, the amounts of IL-1-beta and TNF-alpha produced were - 1000-fold less than those of IL-6 and IL-8. IL-4 alone inhibited the production of IL-1-beta, IL-6, and IL-8 by 32, 35, and 50%, respectively. IL-10 alone was less potent than IL-4 in suppressing these cytokines. Of note, the combination of IL-4 and IL-10 cooperatively exerted potent suppressive effects on the production of IL-1-beta, IL-6, and IL-8 by 74.3, 69, and 77%, respectively. The suppressive effects of the combination of IL-4 and IL-10 on IL-6 and IL-8 were also observed at the levels of mRNA. Conclusion: These results suggest the combination (if IL-4 and IL-10 may be capable of suppressing the production of inflammatory cytokines at rheumatoid inflammatory joints.