Anti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosus
| Autor: | Don E. Griswold, Bailin Liang, Peter J. Bugelski, Xiao Yu R Song, Debra B. Gardner |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_treatment Lymphocyte Immunology Lymphocyte Activation medicine.disease_cause Severity of Illness Index Autoimmune Diseases Autoimmunity Mice Immune system T-Lymphocyte Subsets medicine Animals Lupus Erythematosus Systemic Immunology and Allergy Autoimmune disease B-Lymphocytes Serum Amyloid A Protein Lupus erythematosus Mice Inbred NZB biology Interleukin-6 business.industry Autoantibody Antibodies Monoclonal Original Articles DNA medicine.disease Lupus Nephritis Disease Models Animal Cytokine medicine.anatomical_structure Antibodies Antinuclear Disease Progression biology.protein Antibody business |
| Zdroj: | Immunology. 119:296-305 |
| ISSN: | 1365-2567 0019-2805 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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