PPAR-gamma activation as an anti-inflammatory therapy for respiratory virus infections

Newly emerged influenza viruses have attracted extensive attention due to their high infectivity, proinflammatory actions, and potential to induce worldwide pandemics. Frequent mutations and gene reassortments between viruses complicate the development of protective vaccines and antiviral therapeutics. In contrast, targeting the host response for the development of novel cost-effective, broad-based prophylactic or therapeutic agents holds greater promise. Since inflammation often parallels the development of productive immune responses, virus-induced pulmonary inflammation and injury represents an additional challenge to the development of broad-based immunotherapeutics. Excessive inflammatory responses to respiratory viruses, also known as "cytokine storm," are largely due to immune dysregulation that manifests as proinflammatory cytokine secretion. In addition to modulating lipid and glucose metabolism, peroxisome proliferator-activated receptors (PPAR) play important roles in antagonizing core inflammatory pathways such as NF-kappaB, AP1, and STAT. Their role in regulating inflammatory responses caused by pulmonary pathogens is receiving increasing attention, setting the stage for the discovery of novel applications for anti-diabetic and lipid-lowering drugs. This review focuses on the potential use of PPAR-gamma agonists to downregulate the inflammatory responses to respiratory virus-related pulmonary inflammation.