Anti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from dysregulation of the immune system. Interleukin-6 (IL-6) is a multifunctional cytokine produced by macrophages, monocytes and T and B cells. It stimulates B-cell differentiation/maturation, immunoglobulin secretion, and T-cell functions. Elevated levels of IL-6 in serum, urine and renal glomeruli were detected in patients with active SLE and in murine models of SLE. Our study investigated the role of IL-6 in an SLE-like disease in New Zealand Black/White (NZB/W) F1 mice by administration of an anti-murine IL-6 monoclonal antibody (mAb). Intraperitoneal administration of the anti-IL-6 mAb suppressed the production of anti-dsDNA autoantibody. B-cell proliferation induced by anti-IgM and anti-CD40 was lower in the anti-IL-6 mAb-treated mice, ex vivo studies demonstrated that anti-IL-6 mAb treatment inhibited anti-dsDNA production. Anti-CD3-induced T-cell proliferation and mixed lymphocyte reactions were inhibited by anti-IL-6 mAb treatment, indicating a partial down-regulation of T cells. Histological analysis showed that treatment with anti-IL-6 mAb prevented the development of severe kidney disease. These results suggest that treatment with anti-IL-6 mAb has a beneficial effect on autoimmunity in murine SLE and that autoreactive B cells may be the primary target for anti-IL-6 mAb treatment; its effect on autoreactive T cells is also indicated.
Liang
Bailin
B
Immunobiology, Centocor, Radnor, PA, USA. bliang1@cntus.jnj.com
Gardner
Debra B
DB
Griswold
Don E
DE
Bugelski
Peter J
PJ
Song
Xiao Yu R
XY
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology / Q000628:therapy*; D001402:B-Lymphocytes / Q000276:immunology; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology / Q000628:therapy*; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000032:analysis; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D004247:DNA; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D000685:Serum Amyloid A Protein; D000093242:Interleukin-6 Inhibitors; C494087:Stat3 protein, mouse