According to the US Centers for Disease Control and Prevention (CDC), 50,097 individuals died from influenza and pneumonia in 2010.1 The re-emergence of Influenza A subtype H5N1 (avian flu) in 2003 led to a recognition that vaccines and antiviral agents, which are the current treatments for influenza, may not be sufficient to address a pandemic.
HMG-CoA reductase inhibitors (statins) have recently become a target of investigation for expanding the armamentarium of agents that reduce morbidity and mortality in influenza. An article titled “Treating Influenza with Statins and Other Immunomodulatory Agents” explores this novel approach to seasonal and pandemic influenza.2
The Relationship Between Statins, Pro-Inflammatory Cytokines, and Influenza
The rationale for investigating the utility of statins in treating influenza derives from an exploration of the presence of pro-inflammatory cytokines in both acute coronary syndrome (ACS) and influenza. In ACS, inflammatory changes are “superimposed on chronic underlying inflammation and pathological changes in the coronary circulation.”2 Statins lead to a reduction in circulating levels of pro-inflammatory cytokines and improve endothelial function.3
Epidemiological studies have found that influenza and other acute infections are associated with increased incidence of ACS,4,5 stroke,6 and venous thromboembolism,7 as well as elevations in pro-inflammatory cytokines.8,9 This association was the impetus behind the investigation of the potential role of statins in reducing the pro-inflammatory cytokines of influenza.10
Additionally, chronic low-grade inflammation characteristic of metabolic syndrome, which responds to statin treatment is a risk factor for influenza mortality.2 It is plausible, then, that agents commonly used to reduce pro-inflammatory cytokines in other conditions should also be effective in treating influenza.
Statin Treatment of Pneumonia and Influenza
The potential utility of statins in treating pneumonia and influenza has been demonstrated in several studies. For example, statins have been found effective in reducing rates of hospitalization and death in outpatients with community-acquired pneumonia, and some evidence also suggests utility in reducing mortality in inpatients with pneumonia.2
Another study found that prior statin users admitted to the hospital with pulmonary infections experienced a higher rate of mortality from sepsis or pneumonia when statins were discontinued, versus patients who continued taking statins—11 an effect that might be due to “rebound hypercytokinemia.”2
The effectiveness of outpatient statin treatment has not been as thoroughly examined for influenza hospitalizations and death.2 One large-scale 10-year retrospective cohort study of older adults found that outpatient statin use minimally, but significantly, protects against influenza morbidity. The investigators concluded that public health officials and clinicians should focus on other measures for reducing morbidity and mortality in the next influenza pandemic.12
Other Immunomodulatory Agents
Other than statins, Fedson reviewed several immunomodulatory agents, including corticosteroids, aspirin, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), glitazones, fibrates, and metformin.2 Findings of studies investigating other immunomodulatory agents were mixed and inconsistent, with some showing promise, and others limited by concerns about study design.