Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung

Abstract

Influenza virus infection is considered a major worldwide public health problem. Seasonal infections with the most common influenza virus strains (e.g. H1N1) can usually be resolved, but they still cause a high rate of mortality. The factors that influence the outcome of the infection remain unclear. Here we show that deficiency of IL-6 or IL-6 receptor is sufficient for normally sublethal doses of H1N1 influenza A virus to cause death in mice. IL-6 is necessary for the resolution of influenza infection by protecting neutrophils from virus-induced death in the lung and by promoting neutrophil-mediated viral clearance. Loss of IL-6 results in persistence of influenza virus in the lung leading to pronounced lung damage and, ultimately, death. Thus, we demonstrate that IL-6 is a vital innate immune cytokine in providing protection against influenza A infection. Genetic or environmental factors that impair IL-6 production or signalling could increase mortality to influenza virus infection.

Postinfection A77-1726 Treatment Improves Cardiopulmonary Function in H1N1 Influenza-Infected Mice

“…IL-6 is predominantly proinflammatory, and is often correlated with poor ARDS outcomes in humans (44). However, its effects are pleiotropic, and IL-6 can even be lung-protective in some lung injury models (45)(46)(47). Therefore, without further research, we cannot determine whether the relationship between elevated IL-6 concentrations and improved cardiopulmonary function in A77-treated mice is correlative or causative.…”

Neutrophils: Neglected Players in Viral Diseases

“…1d) (Wang et al, 2008) in a time-and dose-dependent manner (Arnold et al, 1994;Yan et al, 1998;Sakai et al, 2000;Tumpey et al, 2005). In addition, matrix metalloprotease MMP-9 (Bradley et al, 2012), IL-10 (Mutnal et al, 2010), IL-6 (Fenton et al, 2002;Dienz et al, 2012), and IL-1 (Schmitz et al, 2005) were also implicated in the regulation of neutrophil migration upon viral infections.…”

Immune response of mice to non-adapted avian influenza A virus

“…Among these mechanisms are included those stimulating the expression of immune mediators. Cytokine profi le mirrors the infl ammatory reaction of the organism to the virus (van Reeth, 2000;Julkunen et al, 2001;Kaiser et al, 2001;Kaufmann et al, 2001;Dienz et al, 2012,). "Early cytokines" are the fi rst to be produced at the site of infection.…”