Inflammation is an essential host defence against
infection, but can be damaging when excessive. Resolution of
inflammation is an active process, and the pro-resolution effects of
lipoxins, resolvins and protectins have received significant interest. Here, we review emerging data on the role of these
lipid mediators in
infectious disease.
Lipoxins influence host control of Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma cruzi and Plasmodium berghei
cerebral malaria in mice. Their effects are protective in
toxoplasmosis, T. cruzi
infection and
cerebral malaria but detrimental in
tuberculosis; related to the balance between pathogen-control and excessive immune response. Topical
lipoxin abrogates the tissue damage seen in a rabbit model of Porphyromonas gingivalis
periodontitis. The increased virulence of H5N1 influenza A virus in mice correlates with reduced expression of SOCS2, required to mediate the effects of
lipoxin. Mice unable to synthesize
lipoxin suffer increased lung pathology during
respiratory syncytial virus infection.
Protectin suppresses influenza A virus replication in vitro and increases survival in a mouse model of severe
influenza infection. Resolvins were investigated in a number of animal models of systemic
bacterial infection, and were found to enhance phagocytic clearance of bacteria, reduce
inflammation severity, promote neutrophil apoptosis, modulate neutrophil chemotaxis and importantly, reduce mortality. Interestingly, resolvin also enhances the antibacterial effect of
ciprofloxacin and
vancomycin. Topical resolvin application reduces the severity of herpes simplex virus
ocular infection in mice. If the effects of these mediators translate from pre-clinical studies into successful clinical trials, they represent promising new strategies in managing
infectious disease.