Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli

Plasma-derived antithrombin III (ATIII) prevents the lethal effects of Esch erichia coli infusion in baboons, but the mechanisms behind this effect are not clear, In the present study, we evaluated the effects of recombinant h uman ATIII (rhATIII) on the clinical course and the inflammatory cytokine a nd coagulation responses in baboons challenged with lethal dose of E coli. Animals in the treatment group (n = 5) received high doses of rhATIII start ing 1 hour before an E coli challenge, Those in the control group were admi nistered saline. survival was significantly improved in the treatment group (P = .002). Both groups had similar hemodynamic responses to E coli challe nge but different coagulation and inflammatory responses, The rhATIII group had an accelerated increase of thrombin-ATIII complexes and significantly less fibrinogen consumption compared to controls, In addition, the rhATIII group had much less severe thrombotic pathology on autopsy and virtually no fibrinolytic response to E coli challenge. Furthermore, the rhATIII group had a significantly attenuated inflammatory response as evidenced by marked reduction of the release of various cytokines. We conclude that the early administration of high doses of rhATIII improves the outcome in baboons let hally challenged with E coli, probably due to the combined anticoagulation and anti-inflammatory effects of this therapy.