Interleukin 10 cooperates with interleukin 4 to suppress inflammatory cytokine production by freshly prepared adherent rheumatoid synovial cells.
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 expression 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 approximately 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.


CONCLUSIONS
These results suggest that combination of IL-4 and IL-10 may be capable of suppressing the production of inflammatory cytokines at rheumatoid inflammatory joints.
Sugiyama
E
E
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Kuroda
A
A
Taki
H
H
Ikemoto
M
M
Hori
T
T
Yamashita
N
N
Maruyama
M
M
Kobayashi
M
M
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D016207:Cytokines; D018836:Inflammation Mediators; D016753:Interleukin-10; D015847:Interleukin-4