Therapeutic actions of cyclosporine and anti-tumor necrosis factor alpha in collagen-induced arthritis and the effect of combination therapy
| Autor: | Marc Feldmann, Richard O. Williams, Lilia Marinova-Mutafchieva, Ravinder N. Maini, Lesley J. Mason, Claudia Mauri, Susan E. Ross |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
medicine.medical_specialty
business.industry medicine.medical_treatment Immunology Alpha (ethology) Arthritis T helper cell Immunotherapy Pharmacology medicine.disease Endocrinology Immune system medicine.anatomical_structure Cytokine Rheumatology Rheumatoid arthritis Internal medicine Immunology and Allergy Medicine Pharmacology (medical) Tumor necrosis factor alpha business |
| Popis: | Objective. To define the mechanisms of action of 2 novel drugs, cyclosporine and anti-tumor necrosis factor alpha (TNF alpha), in collagen-induced arthritis and to determine the effect of combination therapy.Methods. Type II collagen-immunized DBA/1 mice with established arthritis,were treated with cyclosporine alone, anti-TNF alpha alone, cyclosporine plus anti-TNF alpha, or saline.Results. Cyclosporine was found to ameliorate arthritis, suppress interferon-gamma (IFN gamma) production by CD4+ T cells, and reduce TNF alpha expression in arthritic joints. However, cyclosporine did not directly inhibit TNF alpha production by macrophages, indicating that the decrease in TNF alpha expression observed in vivo was probably an indirect consequence of the reduction in type 1 T helper cell activity. Anti-TNF alpha also reduced IFN gamma production by T cells, indicating that TNF alpha is involved in the cellular immune response to collagen. Combined treatment with cyclosporine plus anti-TNF alpha! had an additive therapeutic effect.Conclusion. Although cyclosporine and anti-TNF alpha target different points in the inflammatory pathway, there is an overlap in the consequences of their actions in vivo. |
| Databáze: | OpenAIRE |
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