Endotoxin Augments Hemodynamic and Metabolic Effects of Formyl-Methionyl-Leucyl-Phenylalanine (FMLP) in Rabbits

Abstract

The chemotactic factor formyl-methionyl-leucyl-phenylalanine (FMLP) when injected in rabbits causes dose-dependent transient hypotension, as well as neutropenia, thrombocytopenia and a decrease in systemic vascular resistance, as previously shown. Since both FMLP and endotoxin are elaborated at sites of infection by certain bacteria, whether they act in concert to produce shock was examined. Animals were pretreated with 380 μg/kg of E. coli endotoxin, 24 hours before the infusion of 10^-9 moles FMLP and were compared with animals pretreated only with saline and administered FMLP. Within 3 min after FMLP, endotoxin-pretreated animals developed a significant fall in MAP (p<0.001) and neutrophils (p<0.001) compared to controls. Statistically significant lactic acidemia, with reduced HCO^-₃ levels also developed in the endotoxin-pretreated group after FMLP injection. These results indicate that endotoxin apparently induces a prepared state, thus facilitating the hemodynamic and cellular effects of FMLP in this model.