Nitric oxide-releasing compounds inhibit the production of interleukin-2,-4 and-10 in activated human lymphocytes

In the present study, we investigated the effects of nitric oxide donors, GEA 3162 (1,2,3,4-oxatriazolium,5-amino-3(3,4-dichlorophenyl)-chloride), GEA 3175 (1,2,3,4-oxatriazolium,3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl) sulfonyl]amino]-, hydroxide inner salt) and S-nitroso-N-acetylpenicillamine (SNAP), on the production of Th1 [interleukin (IL)-2] and Th2 (IL-4 and IL-10) type cytokines in activated human lymphocytes. Lymphocytes were stimulated with concanavalin A or a combination of thapsigargin and phorbol myristate acetate in the absence or in the presence of nitric oxide donors. Concanavalin A induced expression of IL-2 mRNA and production of IL-2, and the combination of thapsigargin and phorbol myristate acetate induced expression of IL-4 and IL-10 mRNAs and production of IL-4 and IL-10. These effects were inhibited by the nitric oxide donors in a dose-dependent manner, GEA 3162 and GEA 3175 being more potent than SNAP on a molar basis. The results show that nitric oxide donors have immunomodulatory properties in both Th1- and Th2-derived responses.