Endotoxin tolerance developed during five consecutive LPS administrations as demonstrated by the attenuated release of proinflammatory cytokines on the fifth day and was associated with less leukocyte and endothelial activation. In contrast to animal and human in vitro data, the attenuated response was not limited to the proinflammatory response, as a similar reduction in the anti-inflammatory cytokines was observed, with the exception of TGF-beta.

In severe sepsis and septic shock, infusion of AP inhibits the upregulation of renal inducible NO synthase, leading to subsequent reduced NO metabolite production, and attenuated tubular enzymuria. This mechanism may account for the observed improvement in renal function.