IL-4 and IFN-gamma mRNA induction in human peripheral lymphocytes specificfor beta-lactam antibiotics in immediate or delayed hypersensitivity reactions

beta-Lactam antibiotics elicit CD4+ and CD8+ T-cell-mediated immune respons es that play a central role in allergic reactions. However, the involvement of a type 1- (Th1 or Tc1) or a type 2-like (Th2 or Tc2) differentiation in drug allergy remains unclear. We investigated the expression of interleuki n 4 (IL-4) and interferon gamma (IFN-gamma) mRNA by quantitative reverse tr anscription and polymerase chain reaction (RT-PCR) in patient-derived perip heral blood lymphocytes following specific in vitro stimulation. Samples we re collected from a total of 19 patients who had developed immediate or del ayed clinical manifestations of hypersensitivity to beta-lactam and from 11 control subjects. peripheral blood mononuclear cells (PBMCs) were stimulat ed with either free antibiotics or antibiotic-human serum albumin (HSA) con jugates. Specific induction of IFN-gamma mRNA expression was observed in 11 of 11 allergic patients with immediate reactions, in 6 of 8 patients with delayed reactions, and in 4 of 11 control subjects. IL-4 mRNA expression wa s induced in 5 of 11 allergic individuals with immediate reactions but in n one of the 8 patients with delayed responses and none of the 11 control sub jects. IL-4 mRNA expression was only induced following activation with free drugs, while IFN-gamma mRNA expression was predominantly induced in CD4+ T cells following stimulation with HSA-conjugated drugs. Immediate-type hype rsensitivity to beta-lactams was not associated with a pure type 2-like res ponse when PBMCs were specifically stimulated in vitro: Some patients with well-documented history of beta-lactam-induced immediate allergic reaction showed a high IFN-gamma response. Contact dermatitis involved Tc1 and Th1 c ells and other delayed hypersensitivity reactions to beta-lactams were rest ricted to Th1 responses.