Ribavirin up-regulates IL-12 p40 gene expression and restores IL-12 levels in Leishmania-treated PBMCs.
Ribavirin, a nucleoside analogue that interferes with viral mRNA synthesis and inhibits the replication of RNA and DNA viruses, has been recently proposed as an effective immune response modulator. In the present report, we studied the effect of ribavirin on IL-12 p40 gene expression in peripheral blood mononuclear cells (PBMCs) of healthy subjects. We also studied ribavirin effects on PBMCs activated with lipopolysaccharide (LPS) and phytohaemagglutinin (PHA) and treated with Leishmania donovani antigens. We provide evidence that ribavirin was able to up-regulate IL-12 p40 gene expression and to restore levels of IL-12 p40 gene expression and IL-12 secretion in fully activated PBMCs that were strongly inhibited by L. donovani antigens. Because effective management of leishmanial disease is usually associated with a prevalent T-helper 1 immune response with elevated production of IL-12,our preliminary results may be of particular interest, provided that they will be confirmed by further in vitro and in vivo studies, when considering a possible use of ribavirin as adjuvant in severe leishmanial disease.
Conte
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Department of Biomedical Sciences, Section of General Pathology, University of Catania, Italy. econte@unict.it
Modica
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Cacopardo
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Messina
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Nigro
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Messina
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics*; D053762:Interleukin-12 Subunit p40; D007893:Leishmania donovani / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D021122:Protein Subunits / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D000953:Antigens, Protozoan; D007155:Immunologic Factors; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D012333:RNA, Messenger; D018664:Interleukin-12; D012254:Ribavirin