Enterotoxic shock in rhesus monkeys. The role of selected bloodborne factors.

Abstract

SUMMARY Staphylococcal enterotoxin B, a protein exotoxin from Staphylococcus aureus, produced progressive hypotension and shock when injected (1 mg/kg, iv) into rhesus monkeys. Plasma levels of factors which have been implicated in the pathogenesis of other types of shock were measured. Endotoxin-like activity was measured by the Limulus lysate technique, fibrin degradation products (FDP) were quantified by electroimmunoassay, and activation of the complement system was assayed by measuring total hemolytic complement. Activation of the intrinsic coagulation cascade was assessed by measuring activated partial thromboplastin time (APTT). Activation of the kinin system was evaluated by measuring prekallikrein activity and kininogen. Myocardial depressant factor (MDF) was measured by paper chromatography. Endotoxin-like activity did not appear in plasma, and the complement system was not activated. The appearance of FDP and a significant trend for prolongation of APTT indicated activation of fibrinolysis and the intrinsic coagulation cascade, and suggested that disseminated intravascular coagulation was occurring. Activation of the kinin system was shown by a progressive and significant depletion of kininogen from 338 ± 37 to 226 ± 22 ng kallidin generated/ml, and a significant depletion of plasma prekallikrein activity from 169 ± 8 to 110 ± 15 tosyl arginine methyl ester (TAMe) esterase U/ml. Analysis of covariance indicated that activation of the kinin system was related to changes in blood pressure. MDF did not increase until immediately before death (increase from 1.08 ± 0.15 to 1.92 ± 0.11 paper chromatographic U//tl, n = 6). We conclude that kinins, MDF, and disseminated intravascular coagulation, but not complement or endotoxin, may contribute to the pathogenesis of enterotoxic shock in rhesus monkeys.ENTEROTOXINS isolated from cultures of Staphylococcus aureus are protein exotoxins (28,000-29,000 daltons, molecular weight) which are capable of producing acute food poisoning in humans 1 and other primates.2 Intravenous (iv) injection of enterotoxins in very small doses in rabbits and monkeys produces lethargy, fever, shock, and death.3 There is evidence that during staphylococcal wound infections and purulent skin lesions, enough enterotoxin is released into the circulation of an infected patient to stimulate synthesis of antibody specific to the toxins produced. 4 Since circulating enterotoxins might contribute to the hypotension and shock often observed in these patients, we decided to study possible mechanisms by which enterotoxin causes circulatory shock.When Josefczyk 4 measured anti-enterotoxin antibodies in normal patients and patients with staph- ylococcal infections, antibody to staphylococcal enterotoxin type B (SEB) was the most common type in each group. SEB has been isolated in purity greater than 99%, 5 and its amino acid sequence has been determined. 6 To help to elucidate the mechanisms by which enterotoxins produce shock, we injected SEB (1 mg/kg, iv) into rhesus monkeys and measured plasma l...

Cellular and Cytokine Responses in the Circulation and Tissue Reactions in the Lung of Rhesus Monkeys (Macaca mulatta) Pretreated with Cyclosporin A and Challenged with Staphylococcal Enterotoxin B

“…The explanation that CsA was insuf ciently inhibitory for cytokine production is consistent with the fact that the disease process was qualitatively similar in the CsSEB monkeys to what had been observed in unprotected monkeys in previous studies. For example, the presence in the blood of all the monkeys of brin degradation products 24 hr after challenge (Table 5) is consistent with what has been found in a previous study of SEB intoxication (46). In addition, the histopathologic features of the illness were similar to those of monkeys in a previous study that were not treated with CsA (Table 7).…”

Aerosolized Staphylococcal Enterotoxin B-Induced Pulmonary Lesions in Rhesus Monkeys (Macaca mulatta)

“…Self-limiting vomiting and diarrhea result from oral administration of SEB, typical of staphylococcal food poisoning. In contrast, both aerosol-exposed and intravenously dosed monkeys develop irreversible hypotension, peripheral pooling of blood, and death following a latent period of variable duration (3,15,24,31). Gross and histopathological pulmonary lesions in monkeys given intravenous SEB are similar to lesions in aerosolexposed monkeys reported here and in previous studies ( 11,31 ).…”

“…The pathogenesis of shock and pulmonary edema in SEB intoxication is incompletely characterized ( 11,24,31 ). Pulmonary edema in monkeys administered intravenous SEB is at least in part due tc increased vascular permeability subsequent to en.…”