Effects of carbamazepine and metabolites on IL-2, IL-5, IL-6, IL-10 and IFN-γ secretion in epileptic patients: the influence of co-medication

• Published in: Pharmacological reports 2011-01, Vol.63 (1), p.86-94
• Main Authors: Mathieu, Olivier, Picot, Marie-Christine, Gelisse, Philippe, Bretone, Hélène, Demoly, Pascal, Hillaire-Buys, Dominique
• Format: Article
• Language: English
• Subjects: acridine; Acridines - pharmacology; Adult; Aged; Anticonvulsants - administration & dosage; Anticonvulsants - metabolism; Anticonvulsants - pharmacology; carbamazepine; Carbamazepine - administration & dosage; Carbamazepine - analogs & derivatives; Carbamazepine - metabolism; Carbamazepine - pharmacology; cytokines; Dibenzazepines - pharmacology; Drug Therapy, Combination; Epilepsy - drug therapy; epileptic patients; Female; Humans; IL-5; Interferon-gamma - blood; Interferon-gamma - metabolism; Interleukins - blood; Interleukins - metabolism; Lamotrigine; Male; Middle Aged; Th1 Cells - immunology; Th2 Cells - immunology; Triazines - administration & dosage; Triazines - pharmacology; valproate; Valproic Acid - administration & dosage; Valproic Acid - pharmacology; Young Adult
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/S1734-1140(11)70402-9

Carbamazepine is a widely used anticonvulsive agent. Its metabolic pathway leads not only to the major active metabolite, carbamazepine-10,11-epoxide, but also to minor terminal metabolites such as iminostilbene and acridine. Carbamazepine is usually well-tolerated, but it may lead to rare, but serious, hypersensitive reactions associated with hypereosinophilia. The mechanisms of hypersensitivity reactions to carbamazepine are still largely unknown, and the implications of the cell-mediated immune response (Th1 pathway) or the humoral immune response (Th2 pathway) are still not understood in these reactions. It is also unclear whether the parent drug or its subsequent metabolites are the primary trigger agent. In our study, we performed ex vivo experiments to evaluate the stimulation of cytokine secretion by carbamazepine, carbamazepine-10,11-epoxide, iminostilbene and acridine. IL-5, IL-6 and IL-10 were quantified as markers of the Th2 pathway, and IL-2 and IFN-γ were used as markers of the Th1 pathway. Blood samples (n=24) were obtained from epileptic patients routinely treated with carbamazepine alone or co-treated with lamotrigine or valproate. The concentrations of cytokines in the plasma were determined before and after 3h stimulation with drugs. We found a significantly positive effect of co-treatment with valproate on the basal level of IL-5 (p