Cytokine-induced inflammation in the ovine teat and udder.

The inflammatory response, as measured by the accumulation of leukocytes and ovine serum albumin, induced by interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), interleukin-beta (IL-8), and granulocyte-macrophage colony stimulating factor (GM-CSF) was studied in lactating ovine udders, and in test cisterns of dry ewes after surgical closure of the passage between the teat and udder cisterns. In the lactating udders, IL-1 beta and TNF-alpha, but not IL-8 and GM-CSF, induced significant accumulation of cells. In the teat cisterns, all four cytokines IL-1 beta, TNF-alpha, IL-8, and GM-CSF induced significant cell accumulation. IL-1 beta was the most potent cytokine. A slight increase in serum albumin, paralleling the changes in leukocyte numbers, was observed after infusion of IL-1 beta and, to some extent, TNF-alpha. The cell accumulation induced by IL-1 beta or TNF-alpha was dose and time dependent in lactating udders, and time-dependent in teat cisterns. The cell numbers were considerably higher in lactating udders than in teat cisterns after infusion with IL-1 beta. The first influx of cells was observed earlier, and the cell numbers peaked earlier in the teat cisterns than in the lactating udders. IL-8 and GM-CSF induced dose and time dependent cell accumulation in teat cisterns only. The differences between lactating udders and teat cisterns may be attributable to the differences in tissue area involved and the number of receptors available, or to dilution of cytokines in milk, or to presence of inhibitory factors. Differences between cytokines in their inflammatory effects may be explained by their modes of action. IL-1 beta and TNF-alpha have a wide range of cellular functions enabling them to induce a more prominent response than IL-8 and GM-CSF. Furthermore, receptors for IL-1 beta and TNF-alpha are present on a larger number of cell types. Finally, the results indicated that the teat cisterns, being the port of entry for udder infections, as well as the lactating udders are capable of a diversified inflammatory response which is important in the defence against udder infections.