IL-6 (Interleukin 6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. Besides, IL-6 signals through a cell-surface type I cytokine receptor complex consisting of the ligand-binding IL-6Rα chain (CD126), and the signal-transducing component gp130 (also called CD130). Particularly, IL-6 trans-signaling via soluble IL-6 receptor (sIL-6R) has emerged as a prominent regulator of inflammation in endothelial cells. Importantly, the study shows that selective inhibition of the IL-6 trans-signaling pathway will attenuate inflammation and subsequent barrier disruption in retinal endothelial cells.

In this article, we will introduce a selective inhibitor of the sIL-6R/IL-6 complex, Olamkicept.

Olamkicept (FE 999301; sgp130Fc) is an optimized fusion protein of the natural sgp130 and IgG1-Fc. Besides, Olamkicept shows a 10–100x greater ability to inhibit IL-6 trans-signaling responses than natural sgp130. Furthermore, Olamkicept specifically inhibits IL-6 trans-signaling by binding to the IL-6/sIL-6R complex. Moreover, Olamkicept (10 µg/mL; 1 h) inhibits IL-6 trans-signaling mediated STAT3 activation in HRECs. Meanwhile, Olamkicept (10 µg/mL, 60 min) inhibits IL-6 trans-signaling-induced increase in H₂O₂ levels in HRECs. In addition, Olamkicept (10 µg/mL, 60 min) inhibits IL-6 trans-signaling-induced apoptosis in HRECs. What’s more, Olamkicept (0-1 µg/mL) inhibits IL-11/recombinant sIL-11R-induced proliferation of Ba/F3-gp130 cells.

Olamkicept also selective blockade of IL-6 trans-signaling in vivo. Such as, Olamkicept (sgp130Fc) (0.01-10 mg/kg, s.c.) increases survival in the cecal ligation and puncture (CLP) sepsis mice model. Besides, Olamkicept (0.5 mg/kg, i.p.) suppresses inflammation and increases survival rate in cecum ligation and puncture (CLP)-induced mice with sepsis.

All in all, Olamkicept is a selective inhibitor of the soluble interleukin 6 (sIL-6R)/IL-6 complex and is a soluble gp130-Fc-fusion-protein and anti-inflammatory agent.

Reference:

[1] Valle ML, et al. Exp Eye Res. 2019 Jan;178:27-36.

[2] Barkhausen T, et al. Crit Care Med. 2011 Jun;39(6):1407-13.

[3] SHI Dan-dan, et al. Basic & Clinical Medicine. 2022, 42 (12): 1895-1899.