Hemin ameliorates influenza pneumonia by attenuating lung injury and regulating the immune response

Abstract

The anti-influenza activity of hemin, an inducer, activator and the substrate of heme oxygenase-1 (HO-1), was examined both in vitro and in vivo. The human lung carcinoma cell line A549 was used to evaluate the in vitro effect of hemin on influenza A virus (IAV) replication. A mouse model was used to examine the in vivo activity of hemin. Observation indexes included survival rate and body weight of mice, virus load and pathological examination of the lungs, and characterization of the systemic and local immune responses. The results showed that hemin could induce HO-1 expression in A549 cells and inhibit IAV replication in vitro. The in vivo results showed that injection of hemin could protect mice from death and body weight loss caused by IAV infection. Hemin was administered both at initial and progressive stages of influenza pneumonia (1 day and 4 days after virus infection, respectively) and showed significant anti-influenza activity under both conditions. However, the results showed that although hemin could induce HO-1 expression in vivo, it could not inhibit IAV replication in vivo. Pathological examination showed that hemin significantly attenuated lung tissue injury caused by IAV. Further study showed that hemin could regulate the immune response to IAV infection by reducing lymphocytopenia and local inflammatory cytokine increases caused by IAV infection. This study shows that hemin has the potential for the treatment of IAV infection and its effect may be due to attenuation of lung injury and regulation of the immune response.

Keywords: Heme oxygenase-1; Hemin; Immune regulation; Influenza virus; Lung injury.