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. 2023 Apr 17:1–16. Online ahead of print. doi: 10.1038/s41577-023-00856-y

Fig. 5. Endogenous and therapeutic buffer system to limit IL-6 signalling.

Fig. 5

The buffer for interleukin-6 (IL-6) in the blood is formed by soluble IL-6 receptor (sIL-6R) and sgp130 (Box 1). a, Under healthy, noninflammatory conditions, the buffer system allows local homeostatic signalling mainly in immune cells and hepatocytes but not in typical tissue cells, smooth muscle cells and endothelial cells. A low level of IL-6 and the buffer system prevents systemic IL-6 signalling. b, Under acute and chronic inflammatory conditions, the buffer system is overloaded and allows systemic IL-6 trans-signalling. c, Therapeutic application of sgp130Fc (soluble gp130–Fc fusion protein) under acute and chronic inflammatory conditions reinforces the buffer system and prevents systemic IL-6 trans-signalling. Coloured shapes have the same meanings as in Fig. 4.