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

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.