Anti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosus

Immunology. 2006 Nov;119(3):296-305. doi: 10.1111/j.1365-2567.2006.02433.x.


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.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / biosynthesis
  • Antibodies, Monoclonal / therapeutic use*
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy*
  • B-Lymphocytes / immunology
  • DNA / immunology
  • Disease Models, Animal
  • Disease Progression
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / therapy*
  • Lupus Nephritis / immunology
  • Lupus Nephritis / pathology
  • Lupus Nephritis / prevention & control
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred NZB
  • STAT3 Transcription Factor / metabolism
  • Serum Amyloid A Protein / analysis
  • Severity of Illness Index
  • T-Lymphocyte Subsets / immunology


  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Interleukin-6
  • STAT3 Transcription Factor
  • Serum Amyloid A Protein
  • Stat3 protein, mouse
  • DNA