PREINCUBATION OF ENDOTOXIN WITH MONOCLONAL ANTI-LIPID-A (E5), BUT NOTIN-VIVO TREATMENT, INHIBITS CIRCULATORY DYSFUNCTION

Monoclonal antibodies (mAb) directed against the toxic lipid A portion of lipopolysaccharide (LPS) have been shown to bind lipid A in vitro, but clinical trials of such mAbs have yielded mixed results. In 53 ra ts instrumented for macrocirculatory and cremaster muscle microcircula tory measurements, we examined whether E5, a murine-derived anti-lipid A mAb, could inhibit LPS-induced circulatory dysfunction when incubat ed with LPS in vitro or given separately in vivo prior to LPS administ ration. Compared with Control rats (Group I), rats infused with 10 mg/ kg Escherichia coil LPS (Group II) displayed marked decreases in arter ial pressure and cardiac output and marked decreases in erythrocyte ve locity in second, third, and fourth order skeletal muscle arterioles. Infusion of 2 mg/kg E5 90 min prior to LPS infusion (Group III) did no t improve cardiovascular performance. In contrast, incubation of LPS w ith either 2 mg/kg (Group IV) or 10 mg/kg (Group V) E5 prior to infusi on significantly attenuated LPS-induced changes in both macrocirculato ry and microcirculatory function, Further investigation of the dispari ty between the in vitro and in vivo neutralizing capacity of anti-lipi d A mAbs may aid interpretation of the variable clinical results achie ved with these preparations.