Effects of Tocilizumab, an Interleukin-6 Receptor Antagonist, on Cytokine Expression and Animal Survival in a Model of Fatal Acute Respiratory Distress Syndrome

Abstract

This study aims to investigate effects of tocilizumab, a monoclonal antibody to interleukin-6 (IL-6) receptors, on cytokine expression and animal survival in a model of fatal acute respiratory distress syndrome (ARDS) characterized by high mortality rates and increased IL-6 production in the lungs. The expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumour necrosis factor (TNF-α) and interferons α (IFN-α) and β (IFN-β) in the lungs was assessed by real-time PCR. Cytokine production was assessed by enzyme immunoassay. Although tocilizumab did not affect the expression of the studied cytokines in the lungs of animals with ARDS, it changed the profiles of their release. An acute multifold increase in the levels of IL-6 in the lungs was observed in the first two hours after the administration of tocilizumab, followed by a decrease of IL-6 to lower values similar to those observed in intact animals. Tocilizumab did not reduce mortality in treated animals with ARDS compared to those without treatment. Thus, the inhibition of the IL-6 receptor signaling pathway alone does not provide an effective solution to the problem of reducing mortality from ARDS associated with the development of a “cytokine storm”.