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Bacterial infections can quickly turn into sepsis, with its attendant clinical sequelae of inflammation, tissue injury, and organ failure. Paradoxically, sustained inflammation in sepsis may lead to immune suppression, because of which the host is unable to clear the existing infection. Use of agents that suppress the inflammatory response may accelerate host immune suppression, whereas use of traditional antibiotics does not significantly affect inflammation. In this study, we investigated whether lipoxin A4 (LXA4), a specialized, proresolution lipid mediator, could increase neutrophil phagocytic activity as well as reduce bacterial virulence. Using the mouse cecal ligation and puncture (CLP) model of sepsis, the administration of LXA4 (7 μg/kg i.v.) 1 h after surgery increased neutrophil phagocytic ability and Fcγ receptor I (CD64) expression. Ex vivo studies have confirmed that the direct addition of LXA4 to CLP neutrophils increased phagocytic ability but not CD64 expression. LXA4 did not affect neutrophils taken from control mice in which CD64 expression was minimal. Taken together with in vivo data, these results suggest that LXA4 directly augments CD64-mediated neutrophil phagocytic ability but does not directly increase neutrophil CD64 expression. Bacterial communication and virulence is regulated by quorum sensing inducers. In Pseudomonas aeruginosa, virulence is induced with release of various virulence factors, by N-3-oxododecanolyl homoserine lactone binding to the quorum sensing receptor, LasR. We show that LXA4 is an inhibitor of LasR in P. aeruginosa and that it decreases the release of pyocyanin exotoxin. These results suggest that LXA4 has the novel dual properties of increasing host defense and decreasing pathogen virulence by inhibiting quorum sensing.-Wu, B., Capilato, J., Pham, M. P., Walker, J., Spur, B., Rodriguez, A., Perez, L. J., Yin, K. Lipoxin A4 augments host defense in sepsis and reduces Pseudomonas aeruginosa virulence through quorum sensing inhibition.

This study aimed to explore how drug-induced pyoderma gangrenosum develops in the body. Pyoderma gangreno-sum (PG) is a rare autoinflammatory disease (a genetic disease caused by a malfunctioning immune system) that causes tissue cells to die, resulting in severe and painful ulcers. Drug-induced disease is where a disease occurs, or is triggered, as a result of taking medication/drugs. In this study 43 cases of patients diagnosed with drug-induced PG were reviewed. The authors found that most of the medications associated with drug-induced PG affected more the one element in the pathway that leads to a person developing drug-induced PG. Abnormal neutrophil migration and function, dysregulated inflammation, keratinocyte apoptosis, and alteration of epigenetic mechanisms were all found to be associated with the development of drug-induced PG. Abnormal neutrophil migration and function refers to the irregular movement and function of a specific type of white blood cell (which forms part of the body's immune system). Dysregulated inflammation refers to an abnormal inflammation response in the body's cells and tissue. Ker-atinocyte apoptosis means the death of keratinocyte cells (the cells that form the majority of the outer layer of skin). Alteration of epigenetic mechanisms means a change to the way in which a cell reads and understands its own genes, which in turn affects how the cell behaves. The authors conclude that, in order to better understand how PG develops, further research is needed into the immune system, epigenetics (the way in which a cell reads and acts upon its genes) and NETosis (a form of cell death).

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