Effect of dose and method of administration of endotoxin on cell mediator release in neonatal calves

Terry C. Gerros From the Departments of Medical Science (Gerros, Semrad) and Medicine (Proctor), School of Veterinary Medicine and School of Medicine, University of Wisconsin, Madison, WI 53706, and Upjohn Laboratories (LaBorde), The Upjohn Co, Kalamazoo, MI 49007.

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Susan D. Semrad From the Departments of Medical Science (Gerros, Semrad) and Medicine (Proctor), School of Veterinary Medicine and School of Medicine, University of Wisconsin, Madison, WI 53706, and Upjohn Laboratories (LaBorde), The Upjohn Co, Kalamazoo, MI 49007.

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Richard A. Proctor From the Departments of Medical Science (Gerros, Semrad) and Medicine (Proctor), School of Veterinary Medicine and School of Medicine, University of Wisconsin, Madison, WI 53706, and Upjohn Laboratories (LaBorde), The Upjohn Co, Kalamazoo, MI 49007.

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Alice LaBorde From the Departments of Medical Science (Gerros, Semrad) and Medicine (Proctor), School of Veterinary Medicine and School of Medicine, University of Wisconsin, Madison, WI 53706, and Upjohn Laboratories (LaBorde), The Upjohn Co, Kalamazoo, MI 49007.

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Summary

The cellular response induced in the host animal by endotoxin contributes 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 the effect of endotoxin dose and method of administration. Thromboxane B2 (TxB2), and 6-keto prostaglandin F (PGF) concentrations and tumor necrosis factor (tnf), and interleukin-1β (il-1β) activities were measured in 34 newborn calves given Escherichia coli endotoxin at dosage of 0 (saline solution), 0.2, 2.0, or 20 μg/kg of body weight, either by iv administered bolus or infusion over 50 minutes. In all groups and at each lipopolysaccharide dosage, mediators peaked in this sequence: TxB2 and tnf, followed by PGF, then il-1β. 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 administered, indicating that the outcome of endotoxemia, in neonatal calves, may be related to the amount of circulating endotoxin.

Summary

The cellular response induced in the host animal by endotoxin contributes 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 the effect of endotoxin dose and method of administration. Thromboxane B2 (TxB2), and 6-keto prostaglandin F (PGF) concentrations and tumor necrosis factor (tnf), and interleukin-1β (il-1β) activities were measured in 34 newborn calves given Escherichia coli endotoxin at dosage of 0 (saline solution), 0.2, 2.0, or 20 μg/kg of body weight, either by iv administered bolus or infusion over 50 minutes. In all groups and at each lipopolysaccharide dosage, mediators peaked in this sequence: TxB2 and tnf, followed by PGF, then il-1β. 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 administered, indicating that the outcome of endotoxemia, in neonatal calves, may be related to the amount of circulating endotoxin.

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