IL-6 ameliorates acute lung injury in influenza virus infection

Abstract

Interleukin 6 (IL-6) is involved in innate and adaptive immune responses to defend against pathogens. It also participates in the process of influenza infection by affecting viral clearance and immune cell responses. However, whether IL-6 impacts lung repair in influenza pathogenesis remains unclear. Here, we studied the role of IL-6 in acute influenza infection in mice. IL-6-deficient mice infected with influenza virus exhibited higher lethality, lost more body weight and had higher fibroblast accumulation and lower extracellular matrix (ECM) turnover in the lung than their wild-type counterparts. Deficiency in IL-6 enhanced proliferation, migration and survival of lung fibroblasts, as well as increased virus-induced apoptosis of lung epithelial cells. IL-6-deficient lung fibroblasts produced elevated levels of TGF-β, which may contribute to their survival. Furthermore, macrophage recruitment to the lung and phagocytic activities of macrophages during influenza infection were reduced in IL-6-deficient mice. Collectively, our results indicate that IL-6 is crucial for lung repair after influenza-induced lung injury through reducing fibroblast accumulation, promoting epithelial cell survival, increasing macrophage recruitment to the lung and enhancing phagocytosis of viruses by macrophages. This study suggests that IL-6 may be exploited for lung repair during influenza infection.

Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19

“…However, suppression but not depletion of the pro-inflammatory IL-1 family and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections for instance, Mice lacking IL-1 signaling expression, elevated viral replication of coronavirus [72]. In addition, IL-6-deficient mice infected with influenza virus exhibited a higher lethality, more body weight loss and had higher fibroblast accumulation and lower extracellular matrix (ECM) turnover in the lungs than their wild-type counterparts [73]. The inflammasome, a cytosolic protein complex that mediates the processing and secretion of pro-inflammatory cytokines, is one of the first responders during viral infection.…”

Critical Adverse Impact of IL-6 in Acute Pneumovirus Infection

“…Specifically, Dienz and colleagues (37) reported that IL-6 2/2 mice succumbed to sublethal doses of influenza A H1N1 in association with apoptosis of antiviral neutrophils in the lung, whereas Lauder and colleagues (38) found that infection of IL-6 2/2 mice with influenza A H1N1 resulted in infiltration of the lungs with monocytes in association with progression to pulmonary edema and respiratory distress due to an inefficient antiviral T cell response. Subsequent studies that focused on the roles of CD4 + T cells, cytotoxic CD8 + T cells, and IL-27, IL-21, and Ab production as well as lung repair mechanisms (39)(40)(41)(42) all identified IL-6 as a protective factor in acute influenza infection.…”

Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

“…In many studies, IL-6 has been shown to increase with exposure to any insult causing acute lung injury to maintain the homeostasis of the inflammatory response [36–38]. The increase in G-CSF and eotaxin along with the increase in CD4 cells in BALF suggest that acute exposure may be leaning toward the Th2 pathway, implicating potential eosinophilic pneumonia with prolonged exposure [39–41].…”