Iloprost treatment reduces TNF-alpha production and TNF-RII expression in critical limb ischemia patients without affecting IL6.
Iloprost, a stable prostacyclin analogue, regulates expression of genes that are involved in inflammation and in cell growth and inhibits the in vitro production of cytokines. We evaluated the effect of an in vivo weekly iloprost treatment on TNF-alpha and IL6 monocyte production (evaluated by ELISA), on monocyte apoptosis (Annexin V/uptake of propidium iodide by flow cytometry) and on peripheral blood mononuclear cell (PBMC) TNF-alpha receptors (TNF-RI and TNF-RII) mRNA expression (RT-PCR) in 14 atherosclerotic critical limb ischemia patients. PBMC were stimulated with LPS for 24h. TNF-alpha production was significantly reduced by iloprost whereas IL6 production was not affected. Iloprost did not accelerate monocyte apoptosis. TNF-RI mRNA expression was not modified by iloprost, whereas TNF-RII mRNA expression was significantly reduced. Our data show that iloprost may have anti-inflammatory effects in addition to the well-known vasodilatatory and anti-aggregant ones.
Di Renzo
M
M
Department of Clinical Medicine and Immunological Sciences, Section of Internal Medicine, Azienda Ospedaliera Universitaria Senese, Siena, Italy. cd28apo@hotmail.com
Pieragalli
D
D
Meini
S
S
De Franco
V
V
Pompella
G
G
Auteri
A
A
Pasqui
A L
AL
D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016285:Iloprost / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism*; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D016285:Iloprost