Tumor necrosis factor-α Production in swine after oral or respiratory challenge exposure with live Salmonella typhimurium or Salmonella choleraesuis

Thomas J. Stabel From the USDA, Agricultural Research Service, National Animal Disease Center, Physiopathology Research Unit, 2300 Dayton Rd, Ames, IA 50010.

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Paula J. Fedorka-Cray From the USDA, Agricultural Research Service, National Animal Disease Center, Physiopathology Research Unit, 2300 Dayton Rd, Ames, IA 50010.

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Jeffrey T. Gray From the USDA, Agricultural Research Service, National Animal Disease Center, Physiopathology Research Unit, 2300 Dayton Rd, Ames, IA 50010.

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SUMMARY

A series of experiments was conducted to document tumor necrosis factor-α (tnf) activity in serum of swine after inoculation with Salmonella spp endotoxin and after oral or respiratory tract challenge exposure with live Salmonella spp. For experiment 1, a potentially lethal dose of S typhimurium endotoxin (25 μg/kg of body weight) was administered iv, and serum tnf activity was measured. High tnf (approx 700 IU/ml) activity at 1 to 2 hours after administration of the inoculum was associated with death, whereas lower tnf (approx 30 IU/ml) activity was associated with a general prolonged state of shock. For experiment 2, pigs were administered a nonlethal dose (5 μg/kg, iv) of either S typhimurium or S choleraesuis endotoxin. Difference in the ability to induce porcine serum tnf activity was not observed between strains. During experiment 3, pigs were inoculated with 104 colony-forming units of S typhimurium χ4232 either orally by gelatin capsule (gc) or by intranasal (in) instillation. A late serum tnf response (17 IU/ml) was measured at 6 weeks after in inoculation. A serum tnf response was not detected in gc-inoculated pigs. All tissues and feces were test-negative for S typhimurium prior to the 6-week tnf response. Serum tnf activity may be related to clearance of S typhimurium after respiratory tract exposure, but it is not important to or indicative of clearance of orally presented S typhimurium in swine. During experiment 4, pigs were inoculated with 106 colony-forming units of S typhimuriumχ4232 similarly as for experiment 3. Challenge exposure with this medium-size dose of inoculum induced a prolonged peak serum tnf response (37 IU/ml) between 2 and 4 weeks after in inoculation. Again, serum tnf activity was not detected in gc-inoculated pigs. Data suggest that clearance of a medium-size dose (106) of inoculum may be influenced by the prolonged higher serum tnf activity. For experiments 5 and 6, pigs were inoculated in with 103, 106, 108, or 109 S choleraesuis χ3246. A measurable, yet statistically nonsignificant, serum tnf response was observed for all doses. Pigs inoculated by gc with 108 S choleraesuis χ3246 had similar results. High doses (> 106) of live S choleraesuis were associated with clinical signs of endotoxic shock. Clearance of S choleraesuis, or lack thereof, did not correlate with serum tnf activity.

SUMMARY

A series of experiments was conducted to document tumor necrosis factor-α (tnf) activity in serum of swine after inoculation with Salmonella spp endotoxin and after oral or respiratory tract challenge exposure with live Salmonella spp. For experiment 1, a potentially lethal dose of S typhimurium endotoxin (25 μg/kg of body weight) was administered iv, and serum tnf activity was measured. High tnf (approx 700 IU/ml) activity at 1 to 2 hours after administration of the inoculum was associated with death, whereas lower tnf (approx 30 IU/ml) activity was associated with a general prolonged state of shock. For experiment 2, pigs were administered a nonlethal dose (5 μg/kg, iv) of either S typhimurium or S choleraesuis endotoxin. Difference in the ability to induce porcine serum tnf activity was not observed between strains. During experiment 3, pigs were inoculated with 104 colony-forming units of S typhimurium χ4232 either orally by gelatin capsule (gc) or by intranasal (in) instillation. A late serum tnf response (17 IU/ml) was measured at 6 weeks after in inoculation. A serum tnf response was not detected in gc-inoculated pigs. All tissues and feces were test-negative for S typhimurium prior to the 6-week tnf response. Serum tnf activity may be related to clearance of S typhimurium after respiratory tract exposure, but it is not important to or indicative of clearance of orally presented S typhimurium in swine. During experiment 4, pigs were inoculated with 106 colony-forming units of S typhimuriumχ4232 similarly as for experiment 3. Challenge exposure with this medium-size dose of inoculum induced a prolonged peak serum tnf response (37 IU/ml) between 2 and 4 weeks after in inoculation. Again, serum tnf activity was not detected in gc-inoculated pigs. Data suggest that clearance of a medium-size dose (106) of inoculum may be influenced by the prolonged higher serum tnf activity. For experiments 5 and 6, pigs were inoculated in with 103, 106, 108, or 109 S choleraesuis χ3246. A measurable, yet statistically nonsignificant, serum tnf response was observed for all doses. Pigs inoculated by gc with 108 S choleraesuis χ3246 had similar results. High doses (> 106) of live S choleraesuis were associated with clinical signs of endotoxic shock. Clearance of S choleraesuis, or lack thereof, did not correlate with serum tnf activity.

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