Seleno-organic compounds induce interferon and tumor necrosis factor in human but not in rat or mouse lymphoid cells.
The seleno-organic compounds are highly active in several anti-inflammatory assays performed in mice and rats. However, they differ from the classical non-steroidal anti-inflammatory drugs including indomethacin despite the fact that both types of drugs are inhibitors of prostaglandins and leukotrienes. Furthermore, ebselen and analogs are potent anti-oxidants in many animal cell cultures. The toxicity of the drugs is low because selenium in their structure is not bioavailable. We have discovered that the seleno-organic compounds induce interferon gamma (IFN-gamma), IFN-alpha, tumor necrosis factor alpha (TNF-alpha) and other cytokines in human peripheral blood leukocytes (PBL). Furthermore, the action of the drugs and PHA or Con A was synergistic. However, ebselen and analogs were found to be inactive as the cytokine inducers in cultured rat or mouse lymphoid cells. In contrast to their effects in human PBL, the drugs even inhibited the production of IFN-gamma after stimulation with PHA or Con A. The inhibition was dose dependent. We suggest that the induction of IFN by ebselen and analogs is species specific and it may depend on interaction of the drugs with a specific receptor and/or signal-transducing system present in human but not in some animal cells.
Inglot
A D
AD
Laboratory of Virology, Polish Academy of Sciences, Wrocław.
Piasecki
E
E
Zaczyńska
E
E
Zielińska-Jenczylik
J
J
D000818:Animals; D001393:Azoles / Q000494:pharmacology; D002478:Cells, Cultured; D004357:Drug Synergism; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology*; D007372:Interferons / Q000096:biosynthesis*; D054833:Isoindoles; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice / Q000276:immunology*; D008807:Mice, Inbred BALB C / Q000276:immunology; D008934:Mitogens; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats / Q000276:immunology*; D017208:Rats, Wistar / Q000276:immunology; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D001393:Azoles; D007369:Interferon Inducers; D054833:Isoindoles; D008934:Mitogens; D016566:Organoselenium Compounds; D014409:Tumor Necrosis Factor-alpha; C042986:ebselen; D007372:Interferons