Role of eicosanoids, histamine, and serotonin in the pathogenesis of Klebsiella pneumoniae-induced bovine mastitis

SUMMARY By inoculating Klebsiella pneumoniae into the teat canals of mammary glands, coliform mastitis was induced experimentally in 6 lactating cows. Release of eicosanoids, histamine, and serotonin in plasma and milk was studied in response to 2 doses of K pneumoniae. A low dose (mean, 5,000 organisms/ml) was inoculated into cows 1 through 4, and a high dose (mean, 200,000 organisms/ ml) was inoculated into cows 5 and 6. Milk and blood samples were collected before inoculation (0 hours), and hourly, from 3 to 24 hours after inoculation. Concentrations of prostaglandin F2α (pgf2α), prostaglandin E (pge), thromboxane B2 (TxB2), histamine, and serotonin were measured in plasma and milk obtained from control (NaCl solution-inoculated) and infected quarters. Fluorometric analysis of milk from infected quarters revealed significantly increased histamine and serotonin concentrations regardless of the dose of K pneumoniae. The mean (± sem) peak concentrations of histamine were significantly (P < 0.01) increased from the preinoculation value of 44 (± 12) ng/ml to 312 (± 104) ng/ml in milk from infected quarters and 72 ( ± 24) ng/ml in milk from control quarters. The mean peak concentration of serotonin increased significantly from the preinoculation concentration of 436 ( ± 37) ng/ml to 1,754 (± 662) ng/ml and 4,867 (± 1,248) ng/ml in milk from control (P < 0.02) and infected (P < 0.001) quarters, respectively. However, serotonin concentration in milk from infected quarters was approximately 2.8 times greater than that in milk from control quarters. Concentrations of pgf2α, pge, and TxB2 in milk and plasma were evaluated by radioimmunoassay. Concentrations of pgf2α increased significantly (P < 0.001) in milk from infected and control quarters. However, the increase in milk from infected quarters was of a greater magnitude than that in milk from control quarters. The mean peak pge and TxB2 concentrations also increased markedly from preinoculation values in milk from control and infected quarters. Because of large individual variations, increases in milk from infected and control quarters were not significantly different from each other. After inoculation, little or no change was observed in plasma concentrations of histamine, serotonin, TxB2, and pge regardless of the K pneumoniae dose, but plasma pgf2α concentration was significantly (P < 0.05) increased to 633 (± 104) pg/ml from the preinoculation concentration of 352 (± 56) pg/ml. For all 6 cows, marked increases were recorded in milk somatic cell counts from infected quarters and body temperature. Compared with low doses, inoculation of high doses of K pneumoniae in cows 5 and 6 induced an early onset of clinical signs and increases of all measured variables including body temperature. However, the severity of signs and increases were independent of the dose of K pneumoniae. Locally generated histamine, serotonin, and pgf20α in milk from infected quarters may constitute putative inflammatory mediators and may be involved locally in the pathogenesis of acute mastitis. However, their role in inducing systemic signs of acute mastitis is doubtful, because only minimal changes were detected in plasma concentrations of all analytes except pgf2α.