EFFECT OF DOSE AND METHOD OF ADMINISTRATION OF ENDOTOXIN ON CELL MEDIATOR RELEASE IN NEONATAL CALVES

The cellular response induced in the host animal by endotoxin contribu tes greatly to the morbidity and mortality of gram-negative infections in bovine neonates. We characterized the temporal sequence, magnitude , and duration of mediator release during endotoxemia and evaluated th e effect of endotoxin dose and method of administration. Thromboxane B -2 (TxB(2)), and 6-keto prostaglandin F-1 alpha (PGF(1 alpha)) concent rations and tumor necrosis factor (TNF), and interleukin-1 beta (IL-1 beta) activities were measured in 34 newborn calves given Escherichia coli endotoxin at dosage of 0 (saline solution), 0.2, 2.0, or 20 mu g/ kg of body weight, either by IV administered bolus or infusion over 50 minutes. In all groups and at each lipopolysaccharide dosage, mediato rs peaked in this sequence: TxB(2) and TNF, followed by PGF(1 alpha), then IL- 1 beta Neither dose nor method of administration affected the sequence of mediator release. The magnitude of eicosanoid reponse to endotoxin was dose-dependent. During induced endotoxemia, duration and /or magnitude of mediator response reflected the dose of endotoxin adm inistered, indicating that the outcome of endotoxemia, in neonatal cal ves, may be related to the amount of circulating endotoxin.