No evidence for paradoxical effects of tocilizumab in rodents

TL;DR

This paper challenges claims that tocilizumab has paradoxical effects in rodents, arguing that the findings are inconsistent with known IL-6 biology.

Contribution

The paper provides a critical analysis refuting paradoxical effects of tocilizumab in rodent models based on established IL-6 biology.

Findings

The results from Weng and colleagues are not compatible with known IL-6 biology.

The evidence provided is insufficient to support paradoxical effects of tocilizumab in rodents.

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine with important functions in health and disease. In order to activate its target cells, IL-6 binds first to the IL-6 receptor (IL-6R), which in turn induces the recruitment and homodimerization of the signal-transducing β-receptor gp130 and the activation of intracellular signaling cascades, including the phosphoinositide 3-kinase (PI3K)-AKT cascade. IL-6 is involved in the pathogenesis of multiple inflammatory diseases, and tocilizumab, a monoclonal antibody that binds to the IL-6R and thus blocks the biological activities of IL-6, is in clinical use worldwide for the treatment of patients with inflammatory diseases, including rheumatoid arthritis. Recently, Weng and colleagues published a paper in Naunyn–Schmiedeberg’s Archives of Pharmacology describing paradoxical effects of tocilizumab when used on murine cells in vitro and in a rat model of acute lung injury in vivo. In this communication, I provide evidence that the results presented by Weng and colleagues are not compatible with what is known about the biology of IL-6 and highlight why the provided evidence is insufficient to believe that tocilizumab shows the reported paradoxical effects in rodents.

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