Desensitization of the acute inflammatory response in skin and mammary gland of sheep.
Desensitization of the inflammatory response was investigated in the mammary glands and skin of sheep. Following twice daily stimulation of non-lactating glands, neutrophil concentrations in inflammatory exudates during the seventh response to endotoxin (1 microgram) and zymosan-activated plasma (1 ml) were 30% and 20% and those in primary responses occurring concurrently in contralateral glands. Cross-desensitization of ZAP was found in non-lactating glands pretreated with endotoxin. In lactating glands, inflammatory responses were examined following daily infusion of endotoxin (1 microgram) and oyster glycogen (50 mg). The neutrophil influx following infusion of each agent declined linearly, with the fourth response being 16% of the first response for both agents. On Day 5, inflammatory responses in contralateral glands receiving an initial challenge were comparable with primary responses on Day 1 in repeatedly stimulated glands. Thus, desensitization was a local phenomenon restricted to the restimulated gland. The return of normal responsiveness to 1 microgram endotoxin occurred after 9 days in glands desensitized by infusion of a single dose of 50 micrograms endotoxin. Accumulation of neutrophils and leakage of plasma were examined in skin sites restimulated with endotoxin and oyster glycogen. Neutrophil accumulation in restimulated lesions was comparable to primary lesions after about 3.5 days for endotoxin and 4.5 days for oyster glycogen. On the other hand, plasma leakage did not return to normal until Day 8 for endotoxin and until after Day 10 for oyster glycogen. The dissociation between neutrophil accumulation and plasma leakage in restimulated skin lesions contrasts with the dependence of plasma leakage on neutrophil migration reported in primary inflammatory lesions. The results suggest that desensitization of the inflammatory response may influence the pathogenesis of bacterial infection.
D000208:Acute Disease; D000818:Animals; D004731:Endotoxins / Q000276:immunology; D005260:Female; D006003:Glycogen / Q000276:immunology; D007108:Immune Tolerance; D007774:Lactation; D008321:Mammary Glands, Animal / Q000276:immunology*; D008413:Mastitis / Q000276:immunology / Q000662:veterinary*; D011247:Pregnancy; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology*; D012867:Skin / Q000276:immunology; D015054:Zymosan / Q000494:pharmacology
D004731:Endotoxins; D006003:Glycogen; D015054:Zymosan