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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