Tumour
necrosis factor (TNF) is known to have procoagulant activity, and platelet depletion is a feature of TNF-mediated systemic inflammatory responses. The aim of this study was to investigate the role of
fibrinogen consumption in the development of TNF-mediated systemic inflammatory responses and in the associated depletion of platelets. Three murine models of TNF-mediated systemic inflammatory responses were examined: the systemic toxicity reactions (STR) induced by TNF or
lipopolysaccharide (LPS) and severe
malaria (SM), a prominently neurological complication of Plasmodium berghei ANKA
infection in susceptible mice. There was an acceleration in the consumption of
fibrinogen during TNF-STR but not during LPS-STR or SM. However, a concomitant reduction in platelet count was found in all conditions. Mice preliminarily depleted in
fibrinogen by treatment with
ancrod, an
enzyme that specifically degrades
fibrinogen, showed no protection against mortality during TNF- or LPS-STR or SM, although they were protected against tissue damage during a modification of the classical local
Shwartzman reaction. During TNF- and LPS-STR platelets were even lower in
ancrod-treated than control mice and during SM they were not significantly different. This study shows that
fibrinogen consumption, although accelerated by the direct injection of TNF, is not necessary for the development of TNF-mediated systemic inflammatory responses in mice, at variance with local pathology, and does not contribute to the associated depletion of platelets.