VENOM IMMUNOTHERAPY MODULATES INTERLEUKIN-4 AND INTERFERON-GAMMA MESSENGER-RNA EXPRESSION OF PERIPHERAL T-LYMPHOCYTES

The mechanism by which specific immunotherapy exerts its beneficial ef fect remains unclear. In order to evaluate the influence of venom immu notherapy on the T-cell cytokine pattern of allergic reactions, we stu died interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) mRNA expres sion of peripheral T lymphocytes from 12 patients undergoing rush veno m desensitization, before treatment at Day 0 (D0), at Day 15 (D15) and Day 90 (D90) after treatment, and from seven controls. Antigen-specif ic T-cell proliferation was also determined. Cytokine mRNA expression was evaluated using in situ hybridization, 24 hr after culture of peri pheral T cells with medium, venom, or an unrelated allergen. Allergen- induced T-cell proliferation decreased at D15 and D90 of rush immunoth erapy (P less than or equal to 0.02). In venom-stimulated cultures of the patient group, there was a decrease in IL-4 mRNA-positive cells at D15 and D90 (P less than or equal to 0.001). Before desensitization, IFN-gamma mRNA expression was lower in patients than in controls and d id not increase after in vitro allergen stimulation. In contrast, afte r immunotherapy, spontaneous IFN-gamma mRNA expression increased, but only at D90 (P less than or equal to 0.001). The cytokine pattern obse rved at D90 after immunotherapy was similar to that observed in contro l subjects. In conclusion, venom immunotherapy induced an altered cyto kine mRNA pattern in allergen-stimulated T cells which was dissociated from the early changes of allergen-induced T-cell responsiveness.