Venom immunotherapy induces monocyte activation

Background Venom immunotherapy (VIT) is an efficient treatment of hymenopte ra venom allergy. The mechanism of VIT is based on the induction of toleran ce of allergen-specific Th2 cells. The mechanisms of this T cell modulation are unknown, and could depend on cytokines produced by other cell types su ch as interleukin (IL)-12, tumour necrosis factor (TNF)-alpha and IL-10 by monocytes. Objective To assess if VIT modifies the monocyte production of IL-12, TNF-a lpha and IL-10 during the 45 first days of treatment. Methods Fourteen patients and seven controls were included. Blood samples w ere taken once in controls and at day (D)1, D30 and D45 of VIT in patients. Monocytes were isolated, cultured with and without lipopolysaccharide (LPS ), and the culture supernatant was harvested. IL-10, IL-12 and TNF-alpha we re assayed in supernatants by ELISA. Results Baseline cytokine levels were not statistically different between p atients and controls. During, treatment, an increase of spontaneous monocyt e production of IL-12 and TNF-alpha was observed at D15 and D45. The produc tion of IL-10 increased at D15 and D45 but not significantly. After LPS-sti mulation, IL-12, TNF-alpha and IL-10 monocyte production was not modified b y VIT. Conclusion VIT induces a monocyte activation characterized by a delayed ove rproduction of IL-12 and TNF-alpha. These cytokines could be relevant to th e inhibition of Th2 cells during VIT. Therefore, VIT-induced tolerance coul d depend not only on the specific action of venom antigens on T cells, but also on a secondary non-specific action of monocytes.