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The role of interleukin 1 (il-1) as an inflammatory mediator during mastitis and the therapeutic effect of recombinant human il-1 receptor antagonist (il-1ra) for bovine mastitis was studied. Cows were intramammarily infused with lipopolysaccharide (25 μg) in 1 mammary gland. Half the cows also received infusions of 5 mg of il-1ra into the same mammary gland just prior to endotoxin infusion and 4, 8, and 12 hours later. After endotoxin infusion, tumor necrosis factor and high il-1 bioactivity were detected in whey from infused glands. Vascular permeability changes and neutrophil accumulation in milk paralleled the appearance of cytokines. A systemic reaction, characterized by pyrexia and an increase in blood cortisol concentration, also were observed. Milk yield was inhibited and milk composition was altered in infused and noninfused glands. The increase in il-1 bioactivity in milk after endotoxin infusion was almost completely prevented in glands receiving il-lra. However, il-lra had no effect on local inflammation, systemic reaction, or impairment in productive performance. These results indicate that il-1 does not mediate its effect within the milk compartment, and suggest either that il-1 is not critical to the mastitic response or that intramammary infusion of il-1ra does not place the antagonist where il-1 interacts with its receptor.

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in American Journal of Veterinary Research



To define causes of increased susceptibility to coliform mastitis after parturition.


12 healthy Holstein cows assigned to 2 groups. Group-1 cows (n = 6) had calved between 6 and 10 days earlier. Group-2 cows (n = 6) were in midlactation.


Cows from each group were paired and challenge exposed with Escherichia coli in 1 mammary gland. Mastitis severity was determined by bacterial concentration in milk, pyrexia, and milk production. Measures of host defense were neutrophil chemotaxis, adhesion molecule expression, leukocyte recruitment, and cytokine production.


After challenge exposure, group-1 cows had more rapid E coli growth, higher peak bacterial concentration, and higher fever. Leukocyte recruitment was poor in 1 group-1 cow that had peracute mastitis. In contrast, leukocyte recruitment in 5 other group-1 cows began sooner than that in group-2 cows. In these group-1 cows, prechallenge-exposure milk somatic cell counts (SCC) were significantly lower than those in group-2 cows. Pre-challenge-exposure SCC were correlated to stimulated CD18 expression (R2 = 0.79), and both measures correlated inversely with bacterial growth rate (R2 = -0.75). Values for tumor necrosis factor α, interleukin 1, and interleukin 8 in group-1 cows after challenge exposure were greater than or equal to those in group-2 cows.


Weak leukocyte recruitment to the mammary gland is associated with increased severity of coliform mastitis. Impaired production of cytokines measured is not a cause of increased susceptibility to coliform mastitis in early lactation.

Clinical Relevance

Low milk SCC after calving may increase susceptibility to severe coliform mastitis. (Am J Vet Res 1996;57:1569–1575)

Free access
in American Journal of Veterinary Research


In Holstein cattle, an inherited disease has been recognized recently in which leukocytes lack surface glycoproteins termed β2 integrins, which are important in cell adhesion processes. This disease is the homologue of leukocyte adhesion deficiency in human beings and has been termed bovine leukocyte adhesion deficiency. The molecular basis of this disease is failure to produce normal CD18. The gene encoding bovine CD18 and its abnormal mutation have been sequenced, allowing specific diagnosis of the condition by DNA amplification by polymerase chain reaction followed by specific endonuclease digestion. This test was applied to formalin-fixed archival tissues from 18 cattle that had been admitted to the veterinary medical teaching hospital between 1975 and 1991 and that had had persistent and severe neutrophilia. Blood samples were collected from 2 additional cattle, and leukocytes from these samples also were tested. Fourteen cattle were confirmed to have been homozygous for the bovine leukocyte adhesion deficiency gene. Cattle with this condition had ranged in age from 2 weeks to 8 months at admission. They typically had had chronic bacterial infections that had failed to respond to or had recurred after conventional treatment. Consistent findings in these cattle included signs of bronchopneumonia, gingivitis, periodontitis, and peripheral lymphadenopathy. Severe neutrophilia, usually without a left shift, was a hallmark of the disease; consistent clinical biochemical findings included hypoalbuminemia, hyperglobulinemia, and hypoglycemia. This disease is important because it mimics common calfhood diseases such as pneumonia and diarrhea, but is ultimately consistently fatal before adulthood.

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in Journal of the American Veterinary Medical Association