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.
Korhonen
Riku
R
The Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland.
Kosonen
Outi
O
Hämäläinen
Mari
M
Moilanen
Eeva
E
D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000037:antagonists & inhibitors*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D007376:Interleukin-2; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide