Effects of anti-IL-6 receptor antibody on human monocytes

Abstract

Objective. To explore the effects of anti-IL-6 receptor antibody, tocilizumab on function of human monocytes.

Methods. Monocytes from healthy donors were cultured in the presence of staphylococcal enterotoxin B (SEB) with pharmacologically attainable concentrations of tocilizumab or control IgG. The expression of IL-6 mRNA was determined using quantitative RT-PCR. The expression of CD80 and CD86 and the induction of apoptosis of monocytes were measured using flow cytometry.

Results. Tocilizumab promoted apoptosis of SEB-stimulated monocytes. The induction of apoptosis of monocytes by tocilizumab were reversed by addition of IgG, but not IgG F(ab’)₂ fragments. Tocilizumab significantly suppressed the expression of CD80, but not that of CD86, on SEB- stimulated monocytes. Finally, tocilizumab significantly suppressed the expression of mRNA for IL-6 of monocytes stimulated with SEB.

Conclusions. These results demonstrate that one of the mechanism of action of tocilizumab involves the induction of apoptosis of monocytes, which requires interaction with Fc receptor on monocytes. Moreover, the data also indicate that tocilizumab inhibit IL-6 production of monocytes at mRNA levels.

Keywords:

• Apoptosis
• IL-6
• Monocytes
• Rheumatoid arthritis
• Tocilizumab

Acknowledgements

This work was supported by Parents’Association Grant from Kitasato University School of Medicine and grants from Mitsubishi Tanabe Pharma Co., Tokyo, Takeda Pharmaceutical Co., Tokyo, and Chugai Pharmaceutical Co., Tokyo, Japan. These grants have no influences on the study design, the collection, analysis, and interpretation of data, the writing of the report, and in the decision to submit the paper for publication.

Conflict of interest

None.