Due to its association with low-quality milk and a decrease in milk production in bovines, mastitis is a major cause of economic loss. Additionally, mastitis can be harmful to suckling newborns and can cause damage to the mammary gland. In mastitic mammary secretions there is a substantial increase in somatic cells, specifically neutrophils. In this study we examined the ability of mastitic and nonmastitic mammary secretions to cause in vitro neutrophil chemotaxis using a microchemotaxis assay. Also, the role of the inflammatory chemokine interleukin-8 (IL-8) in neutrophil recruitment during mastitis was addressed in these in vitro experiments. We found that both nonmastitic and mastitic mammary secretions were chemotactic, not chemokinetic, for neutrophils. The neutrophil chemotactic activity in mastitic, but not nonmastitic, mammary secretions was blocked by anti-IL-8 antibodies. Molecular mass separation of the active components showed that the chemotactic activity of the mastitic secretions was present in the 10-kDa-or-less fraction and was blocked by anti-IL-8 antibodies. These results indicate that IL-8 plays a major role in neutrophil recruitment during mastitis. An understanding of its role will be of help in designing strategies for immunomodulatory therapies for mastitis.

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These lactation stage-dependent changes in TNF alpha levels reflect differential effects that TNF alpha have on involution and prepartum remodeling of the mammary gland of the dam and on gastrointestinal development and immunoregulatory function of the suckling.

Transforming growth factor-beta 1 (TGF-beta 1) is an immuno-modulatory cytokine which has been shown to modulate the activity of T and B cells. We show here that human TGF-beta 1 inhibited stationary cultures of IL-2 dependent CD4+ bovine lymphoblastoid T cells (BLTC) by down-regulating their IL-2 receptor (IL-2R) expression, arresting cells in the G0/G1 compartment of the cell cycle, and inducing these cells to undergo apoptosis. These events were reversed by the addition of a minimal concentration of IL-2 (2U/ml). In the presence of exogenous IL-2, TGF-beta 1 was found to augment the proliferative response of BLTC through up-regulation of IL-2R expression, allow progression of normal cell cycle, and significantly prevent apoptosis. Our data clearly show that IL-2 and TGF-beta 1, when present alone, have contrasting effects on BLTC. TGF-beta 1 down regulates events that are associated with IL-2 mediated signal. But when present together, IL-2 and TGF-beta 1 upregulate activation signals and proliferation of rapidly dividing CD4+T cells.

The findings suggest that TGF-beta is a major immunoregulatory factor in the involuting mammary gland.