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

被引：11

作者：

Tono, Toshihiro ^{[1
]}

Aihara, Satoko ^{[1
]}

Hoshiyama, Takayuki ^{[1
]}

Arinuma, Yoshiyuki ^{[1
]}

Nagai, Tatsuo ^{[1
]}

Hirohata, Shunsei ^{[1
]}

机构：

[1] Kitasato Univ, Sch Med, Dept Rheumatol & Infect Dis, Sagamihara, Kanagawa 2520374, Japan

来源：

MODERN RHEUMATOLOGY | 2015年 / 25卷 / 01期

关键词：

Apoptosis; IL-6; Monocytes; Rheumatoid arthritis; Tocilizumab; RHEUMATOID-ARTHRITIS PATIENTS; MONOCLONAL-ANTIBODY; DOSE-ESCALATION; SYNOVIAL TISSUE; BLOOD MONOCYTES; PLASMA IL-6; TNF-ALPHA; INTERLEUKIN-6; INHIBITION; CYTOKINES;

D O I：

10.3109/14397595.2014.914016

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：79 / 84

页数：6

共 25 条

[11] Infliximab (chimeric anti-tumour necrosis factor α monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate:: a randomised phase III trial [J].

Maini, R ;

St Clair, EW ;

Breedveld, F ;

Furst, D ;

Kalden, J ;

Weisman, M ;

Smolen, J ;

Emery, P ;

Harriman, G ;

Feldmann, M ;

Lipsky, P .

LANCET, 1999, 354 (9194) :1932-1939

[12] Age-related differences in sensitivity of peripheral blood monocytes to lipopolysaccharide and Staphylococcus aureus toxin B in atopic dermatitis [J].

Mandron, Marie ;

Aries, Marie-Francoise ;

Boralevi, Franck ;

Martin, Helene ;

Charveron, Marie ;

Taieb, Alain ;

Davrinche, Christian .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2008, 128 (04) :882-889

[13] Cytokines in the pathogenesis of rheumatoid arthritis [J].

McInnes, Iain B. ;

Schett, Georg .

NATURE REVIEWS IMMUNOLOGY, 2007, 7 (06) :429-442

[14] Mechanisms for cytotoxic effects of anti-tumor necrosis factor agents on transmembrane tumor necrosis factor α-expressing cells [J].

Mitoma, Hiroki ;

Horiuchi, Takahiko ;

Tsukamoto, Hiroshi ;

Tarnimoto, Yasuhiro ;

Kimoto, Yasutaka ;

Uchino, Ayumi ;

To, Kentaro ;

Harashima, Shin-ichi ;

Hatta, Nobuaki ;

Harada, Mine .

ARTHRITIS AND RHEUMATISM, 2008, 58 (05) :1248-1257

[15]

Nishimoto N, 2010, J CLIN EXP MED, V234, P110

[16] Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease [J].

Nishimoto, Norihiro ;

Terao, Kimio ;

Mima, Toru ;

Nakahara, Hideko ;

Takagi, Nobuhiro ;

Kakehi, Takahiro .

BLOOD, 2008, 112 (10) :3959-3964

[17]

Nishina N, 2013, CLIN RHEUMATOL

[18] Reduction of plasma IL-6 but not TNF-α by methotrexate in patients with early rheumatoid arthritis: a potential biomarker for radiographic progression [J].

Nishina, Naoshi ;

Kaneko, Yuko ;

Kameda, Hideto ;

Kuwana, Masataka ;

Takeuchi, Tsutomu .

CLINICAL RHEUMATOLOGY, 2013, 32 (11) :1661-1666

[19] Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-γ [J].

Radstake, TRDJ ;

Roelofs, MF ;

Jenniskens, YA ;

Oppers-Walgreen, B ;

van Riel, PLCA ;

Barrera, P ;

Joosten, LAB ;

van den Berg, WB .

ARTHRITIS AND RHEUMATISM, 2004, 50 (12) :3856-3865

[20] Brief Report: Inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis [J].

Samson, Maxime ;

Audia, Sylvain ;

Janikashvili, Nona ;

Ciudad, Marion ;

Trad, Malika ;

Fraszczak, Jennifer ;

Ornetti, Paul ;

Maillefert, Jean-Francis ;

Miossec, Pierre ;

Bonnotte, Bernard .

ARTHRITIS AND RHEUMATISM, 2012, 64 (08) :2499-2503

← 1 2 3 →