IL-6 blockade preferentially inhibits Th17 differentiation in collagen-induced arthritis.
We examined the time course of cytokine production by CD4 T cells from mice with collagen-induced arthritis (CIA), and we determined the influence of interleukin-6 (IL-6) blockade on cytokine production. CD4 T cells purified from spleen were cultured with both collagen and anti-CD28 antibody for 48 h and the production of interferon-γ (IFN-γ), IL-4, and IL-17 by the cells, secreted into the supernatants, was measured at various time intervals. The production of all these cytokines started 7 days after the first immunization. A marked increase in IFN-γ production was observed after the second immunization, but IL-4 and IL-17 production was not affected by a second immunization. A single injection of anti-mouse IL-6 receptor antibody (MR16-1) on the day of the first immunization suppressed the onset of arthritis. IL-17 production by CD4 T cells from MR16-1-treated mice was significantly lower than that from the control mice. On the other hand, treatment with MR16-1 showed only a tendency to suppress the production of IL-4 and IFN-γ. Injection of MR16-1 on day 21 did not suppress the onset of arthritis. We examined the direct influence of MR16-1 on cytokine production by differentiated CD4 T cells from arthritic mice. Production of IL-4, IFN-γ, and IL-17 was not affected by MR16-1. In conclusion, IL-6 inhibition preferentially suppresses the induction of Th17 cells and does not seem to impact on cytokine production of already differentiated Th17 cells.
Yoshida
Hiroto
H
Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan.
Hashizume
Misato
M
Mihara
Masahiko
M
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D008297:Male; D051379:Mice; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
D016207:Cytokines; D019947:Receptors, Interleukin-6