Grant: Operating Grant

Leukotriene B4 (LTB4) is a natural mediator of host, recognized as a regulator of leukocyte functional responses. We have recently demonstrated that LTB4 can inhibit viral infection in "in vitro" and "in vivo" models. During the course of a phase I clinical study, we observed that administration of LTB4 to humans caused a dose-dependent plasmatic increase in antimicrobial peptides and our preliminary observations indicate that LTB4 induces the release of interferon alpha, a well-known mediator essential for viral clearance. The recent discovery of molecules named pattern recognition receptors (PRRs) has established a major mechanism for innate immune recognition of pathogens, including viruses. New molecules that activate the PRR system were then developed for their potential therapeutic use, including protection of host defense against infectious pathogens. Our research has previously demonstrated that LTB4 can trigger PRR receptors expressed on different populations of human cells to induce the production of antiviral factors including interferon alpha. The present study is then a follow-up of our research. We propose to investigate the action of LTB4 on other classes of PRR and to evaluate whether LTB4 can exert its action through this system to reduce the severity of respiratory illness during influenza infection and also to determine whether LTB4 can restore normal lung functions. These studies will therefore significantly forward our knowledge of the mechanism of LTB4 against viruses and will indicate new directions and approaches for more efficient pharmacological interventions in the treatment of viral infections.