Effect of tumor necrosis factor antibody given to horses during early experimentally induced endotoxemia

Michelle H. Barton From the Departments of Large Animal Medicine (Barton, Bruce, Moore, Norton, Anders, Morris) and Physiology and Pharmacology (Barton, Moore, Morris), College of Veterinary Medicine, University of Georgia, Athens, GA 30628.

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Elizabeth H. Bruce From the Departments of Large Animal Medicine (Barton, Bruce, Moore, Norton, Anders, Morris) and Physiology and Pharmacology (Barton, Moore, Morris), College of Veterinary Medicine, University of Georgia, Athens, GA 30628.

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James N. Moore From the Departments of Large Animal Medicine (Barton, Bruce, Moore, Norton, Anders, Morris) and Physiology and Pharmacology (Barton, Moore, Morris), College of Veterinary Medicine, University of Georgia, Athens, GA 30628.

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Natalie Norton From the Departments of Large Animal Medicine (Barton, Bruce, Moore, Norton, Anders, Morris) and Physiology and Pharmacology (Barton, Moore, Morris), College of Veterinary Medicine, University of Georgia, Athens, GA 30628.

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Brendan Anders From the Departments of Large Animal Medicine (Barton, Bruce, Moore, Norton, Anders, Morris) and Physiology and Pharmacology (Barton, Moore, Morris), College of Veterinary Medicine, University of Georgia, Athens, GA 30628.

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Debra D. Morris From the Departments of Large Animal Medicine (Barton, Bruce, Moore, Norton, Anders, Morris) and Physiology and Pharmacology (Barton, Moore, Morris), College of Veterinary Medicine, University of Georgia, Athens, GA 30628.

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Abstract

Objective

To test efficacy of murine monoclonal, rabbit polyclonal recombinant equine or human tumor necrosis factor-α (rETNF or rHTNF, respectively) antibodies to inhibit native equine tumor necrosis factor (TNF) activity.

Animals

8 and 18 healthy adult horses for parts 1 and 2 of the study, respectively.

Procedures

In part 1, supernates from endotoxin-activated peritoneal macrophages were incubated with various dilutions of each rETNF antibody and subsequently tested for TNF activity. Serum was also obtained from a horse 1 hour after infusion with 20 ng of endotoxin/kg of body weight and was incubated with various dilutions of rabbit polyclonal rHTNF antibody. In part 2, 20 ng of endotoxin/kg was infused in horses during a 30-minute period. Fifteen minutes after the endotoxin infusion was initiated, 1 of 3 preparations was infused: 0.1 mg of rabbit polyclonal rHTNF antibody/kg, 0.1 mg of human IgG/kg, or 500 ml of 5% dextrose. Clinical and hematologic data were collected for 24 hours.

Results

Compared with the monoclonal antibody, the rabbit polyclonal rETNF antibody was more effective in inhibiting TNF activity. The 50% effective doses of the murine monoclonal rETNF, rabbit polyclonal rETNF, and rabbit rHTNF antibodies were 1.8, 0.8, and 0.6 μg of antibody/ml, respectively. In part 2, endotoxin infusion resulted in significant alternations in all variables; however, differences among treatment groups were not significant.

Conclusions and Clinical Relevance

Although murine monoclonal and rabbit polyclonal rETNF or rHTNF antibodies are capable of inhibiting native equine TNF activity in vitro, when given after initiation of endotoxemia, administration of 0.1 mg of rabbit polyclonal rHTNF/kg does not alter the response to infusion of endotoxin. (Am J Vet Res 1998;59:792-797)

Abstract

Objective

To test efficacy of murine monoclonal, rabbit polyclonal recombinant equine or human tumor necrosis factor-α (rETNF or rHTNF, respectively) antibodies to inhibit native equine tumor necrosis factor (TNF) activity.

Animals

8 and 18 healthy adult horses for parts 1 and 2 of the study, respectively.

Procedures

In part 1, supernates from endotoxin-activated peritoneal macrophages were incubated with various dilutions of each rETNF antibody and subsequently tested for TNF activity. Serum was also obtained from a horse 1 hour after infusion with 20 ng of endotoxin/kg of body weight and was incubated with various dilutions of rabbit polyclonal rHTNF antibody. In part 2, 20 ng of endotoxin/kg was infused in horses during a 30-minute period. Fifteen minutes after the endotoxin infusion was initiated, 1 of 3 preparations was infused: 0.1 mg of rabbit polyclonal rHTNF antibody/kg, 0.1 mg of human IgG/kg, or 500 ml of 5% dextrose. Clinical and hematologic data were collected for 24 hours.

Results

Compared with the monoclonal antibody, the rabbit polyclonal rETNF antibody was more effective in inhibiting TNF activity. The 50% effective doses of the murine monoclonal rETNF, rabbit polyclonal rETNF, and rabbit rHTNF antibodies were 1.8, 0.8, and 0.6 μg of antibody/ml, respectively. In part 2, endotoxin infusion resulted in significant alternations in all variables; however, differences among treatment groups were not significant.

Conclusions and Clinical Relevance

Although murine monoclonal and rabbit polyclonal rETNF or rHTNF antibodies are capable of inhibiting native equine TNF activity in vitro, when given after initiation of endotoxemia, administration of 0.1 mg of rabbit polyclonal rHTNF/kg does not alter the response to infusion of endotoxin. (Am J Vet Res 1998;59:792-797)

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