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Abstract
Interleukin-6 (IL-6) is a pleiotropic cytokine with roles in immunity, tissue regeneration,
and metabolism. Rapid production of IL-6 contributes to host defense during infection
and tissue injury, but excessive synthesis of IL-6 and dysregulation of IL-6 receptor
signaling is involved in disease pathology. Therapeutic agents targeting the IL-6
axis are effective in rheumatoid arthritis, and applications are being extended to
other settings of acute and chronic inflammation. Recent studies reveal that selective
blockade of different modes of IL-6 receptor signaling has different outcomes on disease
pathology, suggesting novel strategies for therapeutic intervention. However, some
inflammatory diseases do not seem to respond to IL-6 blockade. Here, we review the
current state of IL-6-targeting approaches in the clinic and discuss how to apply
the growing understanding of the immunobiology of IL-6 to clinical decisions.