Milk lymphocyte anti-adhesion factor, and its role as an anti-microbial [hyperimmune milk anti inflammatory factor, HIMF]

Studies by Stolle Research and Developement Corporation and various collaborating laboratories spanning the past decade provide a body of evidence that milk obtained from cows hyperimmunized against killed bacterial vaccines contains a small molecular weight, non-peptide, orally active, non-species specific molecule that has potent anti-inflammatory biological activity. Hyperimmune milk anti-inflammatory factor (HIMF) blocks the adhesion of circulating lymphocytes to post-capillary venules and their subsequent trans- endothelial migration and limits the participation of neutrophils in the inflammatory reaction. Hyperimmune milk containing HIMF and semi-purified preparations of HIMF have shown to be effective in reducing inflammation using the following inflammation models: rat paw carrageenan-induced edema, staphylococcal mouse mammary gland infection, intradermal and subcutaneous Escherichia coli infection, the reverse passive Arthus reaction, subcutaneous sponge assay for neutrophil emigration from blood vessels, rat experimental pyelonephritis and intravital microscopy of neutrophil adhesion to rat mesenteric vessels. Blockage of lymphocyte adhesion following different routes of administration of semi-purified HIMF in bacterial infection models results in reduced inflammation and tissue damage. In vitro studies confirmed that HIMF blocks CD18-dependent binding of TPA-stimulated cells to protein-coated plates. Non-toxic, orally active HIMF offers great potential for the treatment of neutrophil mediated tissue damage that occurs in response to chronic inflammation associated with auto-immune disease, toxic shock, organ reperfusion, organ transplantation and bacterial and viral infections. Details of the animal experiments used to define the biochemical properties of HIMF and its mechanism of action will be presented and discussed, with emphasis on how this milk biologic may act both independently and synergistically with milk anti-microbial factors to control both inflammation and tissue damage of the neonatal intestine resulting from inflammation of bacterial or viral infectious origin.