IL-6 blockade preferentially inhibits Th17 differentiation in collagen-induced arthritis

Rheumatol Int. 2011 Jan;31(1):127-31. doi: 10.1007/s00296-010-1552-9. Epub 2010 Jul 24.

Abstract

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.

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology*
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Male
  • Mice
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Receptors, Interleukin-6 / immunology
  • Th17 Cells / immunology*

Substances

  • Cytokines
  • Receptors, Interleukin-6