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

Full Abstract

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.

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Author information

Author/s: Liang, Bailin (B); Gardner, Debra B (DB); Griswold, Don E (DE); Bugelski, Peter J (PJ); Song, Xiao Yu R (XY);

Affiliation: Immunobiology, Centocor, Radnor, PA, USA. bliang1(-atsign-)cntus.jnj.com

Journal and publication information

Publication Type: Journal Article

Journal: Immunology (Immunology), published in England. (Language: eng)

Reference: 2006-Nov; vol 119 (issue 3) : pp 296-305

Dates: Created 2006/10/27; Completed 2007/01/17; Revised 2008/11/20;

PMID: 17067309, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Antibodies, Antinuclear - biosynthesis
Antibodies, Monoclonal - therapeutic use
Autoimmune Diseases - blood; immunology; therapy
B-Lymphocytes - immunology
DNA - immunology
Disease Models, Animal
Disease Progression
Interleukin-6 - antagonists & inhibitors; blood; immunology

Lupus Erythematosus, Systemic - blood; immunology; therapy
Lupus Nephritis - immunology; pathology; 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

Associated Chemicals: Antibodies, Antinuclear (0) ; Antibodies, Monoclonal (0) ; Interleukin-6 (0) ; STAT3 Transcription Factor (0) ; Serum Amyloid A Protein (0) ; Stat3 protein, mouse (0) ; DNA (9007-49-2)

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