Applications: Sepsis/Infection

Sepsis is a life-threatening state following heavy systemic bacterial infections. Sepsis can result in septic shock with deadly multiorgan failure. Ironically the dangerous condition during sepsis, although caused by the infecting microorganisms, is not directly due to these but to an overshooting reaction of the innate immune system. This reaction is associated with the release of proinflammatory cytokines, in particular TNF, and interferons. It has been shown in in vitro as well as in animal experiments that preexposure to MALP-2 can alleviate the results of endotoxin, i.e. that MALP-2 can induce endotoxin tolerance. Moreover, in an animal model of peritonitis, a controlled infection of the peritoneal cavity, MALP-2 prolongs survival time and can to some extent effect a total cure. It is likely that MALP-2 influences the outcome of peritonitis in different ways: (i) cells like macrophages which have had contact with MALP-2 acquire a transient unresponsiveness to endotoxin and other toll-like receptor agonists, most of which are bacterial products. The release of harmful proinflammatory cytokines is thus reduced. (ii) MALP-2 causes infiltration of leukocytes which fight the infection (iii) by acting as an adjuvant MALP-2 finally leads to a specific immune response.

One could envisage that treatment with MALP-2 before or during surgery in cases with high risk of infections could (i) alert the innate immune system before the infection has had the time to spread, and (ii) reduce the overshooting production of harmful proinflammatory cytokines.

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