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Rationale for interleukin-6 blockade in systemic lupus erythematosus

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

P E Lipsky

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

G G Illei

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, illeig{at}mail.nih.gov

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 associationbetween 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.

Key Words: autoimmunity • biologic therapy • cytokines • experimental treatment

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