title: Effects of cyclic GMP-agonists on cyclosporin-induced suppression of human lymphokine production.
abstract: Cyclosporin (Cs) inhibits the elaboration of the lymphokine leukocyte migration inhibitory factor (LIF) from human blood mononuclear cells (MNC) stimulated with recall antigen. This inhibition was counteracted by 3 X 10(-5) M dibutyryl-cyclic GMP and 8-bromo-cyclic GMP and by the cyclic GMP-agonists, sodium nitroprusside (NaNPr), ascorbic acid (As A), sodium azide (NaN3) and carbacholine. Using 5 X 10(-5) M NaNPr, 1 X 10(-3) M NaN3, or 3 X 10(-3) M As A, 25-50-, 4-8- and 2-3-fold elevations of MNC and T-lymphocyte cyclic GMP-levels were obtained independently of the presence of Cs. NaNPr was the most potent of these three cyclic GMP-agonists in counteracting the effect of Cs. The results indicate that intracellular cyclic GMP is a major factor involved in the reversal of Cs-induced inhibition of LIF-production. None of the cyclic GMP-analogues or -agonists by themselves possessed Interleukin 1-like activity, measured by their ability to induce LIF-production by macrophage-depleted T-lymphocytes challenged by recall antigen.
mesh_terms: D000328:Adult; D001205:Ascorbic Acid / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000097:blood*; D003524:Cyclosporins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007961:Leukocyte Migration-Inhibitory Factors / Q000096:biosynthesis*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis*; D009599:Nitroprusside / Q000494:pharmacology; D019810:Sodium Azide; D014373:Tuberculin / Q000276:immunology
chemical_list: D001386:Azides; D003524:Cyclosporins; D007961:Leukocyte Migration-Inhibitory Factors; D008222:Lymphokines; D014373:Tuberculin; D009599:Nitroprusside; D019810:Sodium Azide; D006152:Cyclic GMP; D001205:Ascorbic Acid