SENSITIZATION OF THE BOVINE MAMMARY-GLAND TO ESCHERICHIA-COLI ENDOTOXIN

The effect of repeated infusions of Escherichia coli endotoxin on the acute phase response in the bovine mammary gland was assessed through the concentrations of tumor necrosis factor alpha (TNF-alpha) in milk. Four clinically normal lactating cows received two intramammary infus ions of E coli endotoxin (33 mu g) 24 h apart in the same mammary quar ter. Alone with the second infusion, the cows received one dose of end otoxin in the contralateral quarter. Milk was collected at varying int ervals before and after infusion and TNF-alpha concentrations were det ermined by ELISA. Following the first infusion at 0 h, the mean concen trations of TNF-alpha augmented from undetectable concentrations to a maximum of 0.4 ng/mL at 4 h and declined to below 0.04 ng/mL at 24 h, the time of the second infusion. In the quarters challenged twice, the increase in TNF-alpha concentrations was abrupt, culminating at 11.7 ng/mL 6 h later (at 30 h). The increases in TNF-alpha concentrations w ere similar in the contralateral quarters infused once. TNF-alpha conc entrations in the control, uninfused quarters of infused cows remained undetectable (< 0.04 ng/mL). Despite the low TNF-alpha response follo wing the first infusion, mean somatic cell counts increased markedly, bring only slightly lower than after the second infusion (10(7)/mL and 5 x 10(7)/mL at 8 h and 32 h, respectively) in the quarters challenge d twice. After the first infusion, none of the cows developed fever, b ut following the second infusion, rectal temperature increased markedl y, culminating 6 h after the second infusion. These results show that an infusion in one quarter of an amount of endotoxin sufficient to ind uce a pronounced cell recruitment but insufficient to induce a marked TNF-alpha secretion following the first infusion sensitized not only t hat quarter but also the contralateral one to a second infusion with t he endotoxin. It is thus possible that sensitization of the whole udde r follows a first contact with a moderate dose of endotoxin in one qua rter.