Interleukin 1 and tumor necrosis factor-alpha synergistically increase the production of interleukin 6 in human synovial fibroblast.
We have previously reported that synovial cells could participate in B cell differentiation processes in rheumatoid arthritis (RA) by producing interleukin-6 (IL-6) spontaneously or in response to interleukin-1 (IL-1) stimulation. In this paper, we examined the effects of tumor necrosis factor-alpha (TNF-alpha) on IL-6 production by human synovial fibroblasts. TNF-alpha, as well as IL-1, is a putative relevant molecule in the inflammatory process and in articular destruction in RA. Both IL-1 and TNF-alpha induced IL-6 production by synovial fibroblasts in a dose dependent manner. When synovial fibroblasts were stimulated by IL-1 and TNF-alpha in combination, IL-6 production increased synergistically after 48 hr of a 72 hr culture period. Kinetic studies revealed that the presence of both cytokines at the early phase of stimulation was required for the synergistic effect. These results suggest that TNF-alpha could be involved in a cytokine network in the affected joints of RA and could contribute synergistically with IL-1 to the IL-6 production by synovial fibroblasts in vivo.
Harigai
M
M
First Department of Medicine, National Defense Medical College, Saitama, Japan.
Hara
M
M
Kitani
A
A
Norioka
K
K
Hirose
T
T
Hirose
W
W
Suzuki
K
K
Kawakami
M
M
Masuda
K
K
Shinmei
M
M
D001172:Arthritis, Rheumatoid / Q000276:immunology; D002478:Cells, Cultured; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha