Eosinophil cationic protein and histamine after intestinal challenge in patients with cow's milk intolerance

Background: Mast cells and eosinophils are key cells in the development of active symptoms in allergic diseases and other inflammatory conditions, and they mediate their action through the release of very potent granule constituents. Methods: Five patients with milk-related gastrointestinal symptoms diagnosed by double-blind placebo-controlled milk challenges, but with negative responses to skin prick tests and RASTs with milk, and eight healthy control subjects were investigated. Repeated perfusion studies were performed with a two-balloon, six-channel tube by using milk, casein, and whey as antigens. Luminal eosinophil cationic protein, histamine, and albumin were measured by radioimmunoassay. Results: Luminal cow's milk induced a pronounced increase in intestinal secretion of histamine and eosinophil cationic protein in patients, but not control subjects, during the first 20 minutes after challenge (histamine from 123 +/- 12 to 543 +/- 175 ng/cm, hr; eosinophil cationic protein from 80 +/- 23 to 686 +/- 262 ng/cm, hr). Albumin, as a marker of plasma leakage, was also significantly increased. Conclusion: These data indicate that mast cells and eosinophils are effector cells not only in patients with allergic disease but also in patients intolerant to foods and lacking circulating antibodies. The underlying mechanisms may be a reaction mediated by locally appearing antibodies or an immunologic activation resembling that found in intestinal disorders such as celiac disease.