SARS-CoV-2 and COVID-19: Is interleukin-6 (IL-6) the 'culprit lesion' of ARDS onset? What is there besides Tocilizumab? SGP130Fc

Abstract

Since the outbreak of COVID-19 many studies have been published showing possible therapies, here the author discusses the end of stage disease related drugs, like Tocilizumab which is currently being used in ARDS patients. In some patients, disease progression leads to an enormous secretion of cytokines, known as cytokine storm, among those cytokines IL-6 plays an important role. Here the author shows how IL-6 has both pro and anti-inflammatory properties, depending on the pathway of transduction: soluble (trans-signaling) or membrane-related (classic signaling), and suggests how targeting only the pro-inflammatory pathway, with SGP130Fc, could be a better option then targeting them both. Other possible IL-6 pathway inhibitors such as Ruxolitinib and Baricinitib are then analyzed, underlying how they lack the benefit of targeting only the pro-inflammatory pathway.

Keywords: Baricitinib; COVID-19; Coronavirus; Coronaviruses; Drugs; IL-6; IL-6 trans-signaling; Interleukin-6; Ruxolitinib; SARS-CoV-1; SARS-CoV-2; SGP130Fc; Strategies; Targets; Therapies; Tocilizumab.

Fig. 1

This diagram shows the classic signaling pathway (mediated by the membrane-bound form of IL-6 receptor, mIL6R) which is believed to be the anti-inflammatory one and the trans-signaling pathway (mediated by the soluble form of IL-6 receptor, sIL6-R) which is believed to be the pro-inflammatory one. Tocilizumab inhibits both of them, SGP130Fc inhibits only the trans-signaling pathway.