Rationale for interleukin-6 blockade in systemic lupus erythematosus.
Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities that plays an important role in immune regulation and inflammation. Among other actions, it induces terminal differentiation of B lymphocytes into antibody-forming cells and the differentiation of T cells into effector cells. IL-6 also has multiple potent proinflammatory effects. An association between IL-6 and lupus was demonstrated in murine models of SLE and blocking IL-6 improved lupus in all models tested. Data from several studies suggest that IL-6 plays a critical role in the B cell hyperactivity and immunopathology of human SLE, and may have a direct role in mediating tissue damage. Based on these data, we propose that blocking the effect of IL-6 in humans may improve lupus by interacting with the autoinflammatory process both systemically and locally.
Tackey
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Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, USA.
Lipsky
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PE
Illei
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GG
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D019947:Receptors, Interleukin-6 / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors