The time-course of milk antigen-induced TNF-α secretion differs according to the clinical symptoms in children with cow's milk allergy

Background: TNF-alpha secretion by blood mononuclear cells stimulated with cow's milk proteins is significantly higher in infants with active cow's milk allergy (CMA) manifested by digestive symptoms than in children who have recovered from CMA. Objective: The current study was undertaken to analyze the kinetics of TNF-alpha secretion and to evaluate the usefulness of the measurement of TNF-alpha release in whole blood cultures in the prediction of clinical outcome after milk challenge, Methods: Blood samples were obtained from 83 children maintained on a cow's milk-free diet and examined just before a cow's milk provocation. Children were divided into 4 groups according to clinical outcome: group I (active CMA with cutaneous symptoms), group II (active CMA with predominantly digestive symptoms), group III (children recovered from CMA), and group IV (control), The kinetics of TNF-alpha secretion was measured in blood cultured for 1 to 5 days at different cow's milk protein concentrations, Results: On day 1 TNF-alpha secretion was significantly higher in group I (485 [453] pg/mL, mean [SD], P < .005) and in group II (269 [102] pg/mL, P < .005) than that observed in groups III and IV (149 [95] and 87 [71] pg/mL, respectively). Then TNF-alpha was rapidly degraded and a second peak of secretion was observed on day 5 but only in group II (278 [221] pg/mL), whereas in groups I, III, and IV a low secretion was observed (70 [61], 45 [40], and 11 [12] pg/mL, respectively, P < .02), Conclusion: These results show that the pattern of TNF-alpha secretion in response to cow's milk proteins is different in CMA infants with cutaneous or digestive symptoms and suggest that TNF-alpha release might predict clinical relapse on challenge.