EFFECT OF TERFENADINE ON TNF-ALPHA RELEASE FROM PERIPHERAL-BLOOD MONONUCLEAR-CELLS DURING COWS MILK ALLERGY

Background In infants with cow's milk allergy and intestinal symptoms, peripheral blood mononuclear cells stimulated in vitro with cow's mil k proteins, secrete large amounts of the proinflammatory cytokine TNF alpha thus altering intestinal barrier capacity. Terfenadine, an antih istaminic drug, inhibits the release of several inflammatory mediators , including histamine, prostaglandins and leukotrienes. Objectives To test the potential ability of terfenadine to inhibit TNF alpha secreti on by mononuclear cells from infants with cow's milk allergy. Methods Mononuclear cells from infants allergic to cow's milk proteins were st imulated in vitro for 6 days by a mixture of milk proteins (beta-lacto globulin, alpha-lactalbumin and casein) with or without terfenadine (0 .1-1 mu M) and culture supernatants were assayed for TNF alpha by enzy me immunoassay. The effect of culture supernatants on intestinal barri er capacity was evaluated by measuring the electrical resistance (inde x of integrity) of filter-grown HT29-19 A intestinal cells in Ussing c hambers. Results During active cow's milk allergy, mononuclear cells s timulated with cow's milk proteins secreted large amounts of TNF alpha which significantly reduced the electrical resistance of HT29-19 A in testinal cells. There was a dose-dependent decrease in TNF alpha secre tion in the presence of terfenadine, with a maximal inhibition of 62% of this secretion at 1 mu M. Accordingly, terfenadine-treated mononucl ear cells supernatants did not alter the electrical resistance of inte stinal HT29.19 A cells, Conclusion These results indicate that in infa nts with intestinal dysfunction due to cow's milk allergy, terfenadine is a potent inhibitor of the TNF alpha secretion induced by sensitizi ng milk protein antigens. This inhibition prevents the degradation of intestinal function as measured in an intestinal cell line, in vitro.