Humoral factors in primate endotoxin shock

Many biologically active substances are released from the cell in endotoxic shock and thought to contribute to morbidity and mortality. Whether or not these substances are independently toxic or require endotoxin as a catalyst is uncertain; 20 mg/kg E. coli endotoxin was infused into seven rhesus (R) macaca monkeys (toxin donor). Seven R macaques received an equivalent volume of normal saline (control donor). Animals were monitored for 12 h and lactated Ringer's was infused to maintain a minimum MABP of 40 mmHg. Donor animals were exsanguinated; plasma was extracted and a Limulus lysate assay (LAL) was utilized to determine the approximate amount of endotoxin present in toxin donor plasma. This volume of endotoxin (0.125 mg/kg) was added to control donor plasma. Plasma was infused into seven toxin receivers and six control receivers. Receiver animals were monitored for 24 h and killed after 3 d. Lungs were evaluated histologically for evidence of acute injury. Five of the seven toxin receivers and no control receivers died within 3 d (P less than .005). Significantly more hemorrhage occurred in toxin receivers (P less than .01). Our data suggest a humoral factor present in the plasma of toxin donor capable of promoting tissue injury and death of recipient animals independent of endotoxin.