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.
Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine , Kanagawa , Japan.
Toshihiro
T
Tono
Satoko
S
Aihara
Takayuki
T
Hoshiyama
Yoshiyuki
Y
Arinuma
Tatsuo
T
Nagai
Shunsei
S
Hirohata
D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000276:immunology*
D061067:Antibodies, Monoclonal, Humanized; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007074:Immunoglobulin G; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C502936:tocilizumab
Apoptosis; IL-6; Monocytes; Rheumatoid arthritis; Tocilizumab