Excessive production of interleukin (IL)-4, IL-13 and interferon (IFN)- γ is thought to be important in the development of allergic disease and atopy. Several investigators have linked the IL-4 and IL-4R genes to allergic disease and atopy. The aim of this study is to further explore the mechanism of penicillins allergy and evaluate the possible role of the IL-4 C-589T and IL-4R αQ576R polymorphisms in modulating the allergic responses to penicillins. Radioallergosorbent test (RAST) was used to detect eight kinds of specific immunoglobulin E (IgE) to penicillins in serum. Serum levels of IL-4, IL-13 and IFN- γ were measured by using enzyme-linked immunosorbent assay (ELISA). The IL-4 C-589T and IL-4R αQ576R polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP). Compared with control subjects, there were significantly higher levels of IL-4, IL-13 and IFN- γ in allergic patients with positive specific IgE ( P < 0.01), and the lower levels of IL-4 and IFN- γ were observed in allergic patients with negative specific IgE ( P < 0.05). We found a growing trend of IL-4 and IL-13 levels with the kind increasing of positive specific IgE, and even there were significant correlations between the three kinds of cytokines and many kinds of specific IgE ( P < 0.05). The IL-4R α*Q576 allele was significantly increased in patients with penicillins allergy compared with control subjects ( P < 0.01). Furthermore, the allele was strongly associated with increased serum-specific benzylpenicilloyl (BPO)-, phenoxomethylpenicillanyl (PVA)- or ampicillanyl (APA)-IgE levels in patients with positive specific IgE ( P < 0.05). These data suggest that IL-4, IL-13 and IFN- γ play an important roles in penicillins allergy. The IL-4R αQ576R polymorphism may involve in the development of penicillins allergy, and through modulating specific serum IgE levels. [ABSTRACT FROM AUTHOR]