Quercetin suppresses pro-inflammatory cytokine release in human respiratory cells infected with rhinovirus and morbidity and mortality in mice infected with influenza virus

The innate immune response is an important mediator of symptoms caused by many respiratory viruses. Oxidative stress appears to play a role in this host response. Quercetin is a flavonoid present in a variety of fruits and vegetables and has been shown by us and others to have potent antioxidant and anti-inflammatory activity in both in vitro and in vivo models. The adsorption, distribution, metabolism, and excretion of quercetin have been extensively studied in laboratory animals and humans. We have demonstrated that following oral ingestion as much as 60% of the dose is adsorbed and rapidly conjugated in the intestinal epithelium and first pass through the liver to its methylated, sulfated, or glucuronidated forms. These conjugates have comparable bioactivity to quercetin aglycone and are systematically adsorbed across all major tissues with the highest concentration in pulmonary tissue. This study examined the effects of quercetin on cytokine release in human respiratory cells infected with rhinovirus and in mice infected with influenza A virus. Human respiratory cells were maintained in the presence of quercetin (25µg/ml) and infected with rhinovirus type 39at either a high or low multiplicity of infection. Supernatants collected at an early (6 hours) or late phase (30 hours) following infection were assayed for release of infectious virus and IL-8, a pro-inflammatory cytokine responsible for recruitment of polymorphonuclear leukocytes. Quercetin had little effect on early phase IL-8 release; however, late phase IL-8 expression was significantly reduced. Virus replication was not affected at either early or late times after infection. We have previously demonstrated that exercise stress increases the susceptibility of mice to infection with influenza virus. This study evaluated quercetin effects in mice run to exhaustion on 3 consecutive days prior to infection with 1 LD-50 of influenza A/Puerto Rico/8/34 (H1N1) virus. Mice receiving 12.5mg/kg of quercetin daily by gavage for 7 days prior to intranasal infection had a significant (P<0.05) reduction in morbidity and mortality on days 5–7 post-infection. Our study provides preliminary evidence to suggest that quercetin can suppresses pro-inflammatory cytokine release and thereby reduce symptom severity in respiratory virus infections.