Rheumatology Medical News about tocilizumab;inti-inflammatory mechanism

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Anti-inflammatory mechanism of tocilizumab, a humanized anti-IL-6R antibody: Effect on the expression of chemokine and adhesion molecule
Rheumatology International, 05/29/09

Suzuki M et al. – Data suggest that IL-6 signaling plays an important role in inflammatory cell migration by increasing the rate of cell adhesion and by inducing chemokine production in inflamed joints.

Methods

Aim was to examine the influence of IL-6 on chemokine production from:
- peripheral blood mononuclear cells (PBMC)
- fibroblastic synovial cells and
- human umbilical vessel endothelial cells (HUVEC)
Effect of IL-6 on the adhesion of U937 cells to HUVEC was also examined
For chemokine production, PBMC, fibroblastic synovial cells and HUVEC were cultured with IL-6 or IL-6 + soluble IL-6R (sIL-6R) for 24 h
Production of MCP-1 and IL-8 were measured in supernatants
Soluble adhesion molecules in HUVEC culture supernatant were measured by ELISA
Expression of adhesion molecules on cell surface were examined by flow cytometry analysis

Results

IL-6 and IL-6 + sIL-6R induced production of both MCP-1 and IL-8 in PBMC and synovial cells, respectively.
In HUVEC, IL-6 + sIL-6R induced MCP-1 production, but inhibited IL-8 production
Soluble ICAM-1 was detectable in IL-6 + sIL-6R-treated HUVEC
IL-6 + sIL-6R-induced ICAM-1 expression on cell membrane of HUVEC
Adhesion of U937 cells to HUVEC was augmented when HUVEC was pretreated by IL-6 + sIL-6R
This adhesion was suppressed by anti-ICAM-1 Ab and anti-IL-6R Ab, but not by Abs against VCAM-1 or E-selectin

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