Effect of terfenadine on TNFα release from peripheral blood mononuclear cells during cow's milk allergy

Summary Background In infants with cow's milk allergy and intestinal symptotns, peripheral blood mononuclear cells stimulated in vitro with cow's milk proteins, secrete large amounts of the proinflammatory cytokine TNFα thus altering intestinal barrier capacity. Terfenadine, an antihistaminic drug, inhibits the release of several inflammatory mediators, including histamine, prostaglandins and leukotrienes. Objectives To test the potential ability of terfenadine to inhibit TNFα secretion by mononuclear cells from infants with cow's milk allergy. Methods Mononuclear cells from infants allergic to cow's milk proteins were stimulated in vitro for 6 days by a mixture of milk proteins (β‐lactoglobulin, α‐lactalbumin and casein) with or without terfenadine (0.1 –1 μM) and culture supernatants were assayed for TNFα by enzyme immunoassay. The effect of culture supernatants on intestinal barrier capacity was evaluated by measuring the electrical resistance (index of integrity) of filter‐grown HT29–19 A intestinal cells in Ussing chambers. Results During active cow's milk allergy, mononuclear cells stimulated with cow's milk proteins secreted large amounts of TNFα which significantly reduced the electrical resistance of HT29–19 A intestinal cells. There was a dose‐dependent decrease in TNFα secretion in the presence of terfenadine, with a maximal inhibition of 62% of this secretion at 1 μM. Accordingly, terfenadine‐treated mononuclear cells supernatants did not alter the electrical resistance of intestinal HT29. 19 A cells. Conclusion These results indicate that in infants with intestinal dysfunction due to cow's milk allergy, terfenadine is a potent inhibitor of the TNFα secretion induced by sensitizing milk protein antigens. This inhibition prevents the degradation of intestinal function as measured in an intestinal cell line, in vitro.