Pentoxifylline in vivo and in vitro down-regulates the expression of the intercellular adhesion molecule-1 in monocytes.
Since pentoxifylline (PTX) was recently recognized as a substance with antiinflammatory capacities, we studied the in vivo and in vitro effect of PTX on the expression of the intercellular adhesion molecule-1 (ICAM-1) on human monocytes. For this purpose four healthy volunteers were treated with PTX (5 x 400 mg/day) for 2 days. Monocytes were isolated before and after PTX treatment and ICAM-1 expression was investigated. As shown by fluorescence-activated cell sorter (FACS) analysis, cultured monocytes isolated after oral application of PTX expressed significantly decreased amounts of ICAM-1 when compared with monocytes collected prior to oral PTX application. Northern blot analysis revealed reduced amounts of ICAM-1 mRNA in monocytes derived from volunteers after oral PTX treatment in comparison with monocytes isolated before oral PTX administration. Similarly, in monocytes treated with PTX (200 micrograms/ml) in vitro ICAM-1 was found decreased both at the protein and mRNA level in comparison with untreated cells. The inhibitory effect of PTX on ICAM-1 expression in monocytes could be reversed by the addition of exogenous tumour necrosis factor-alpha (TNF-alpha; 200 U/ml) suggesting that ICAM-1 down-regulation is mediated secondary to TNF-alpha suppression by PTX. The specific role of TNF-alpha in mediating ICAM-1 expression in cultured monocytes could be confirmed by the finding that a neutralizing anti-TNF-alpha antibody partially down-regulated ICAM-1 expression. The observed suppressive in vivo and in vitro effects of PTX on ICAM-1 expression in monocytes may contribute to the recently described antiinflammatory effects of PTX, e.g. in sepsis or allergic contact dermatitis.
Neuner
P
P
Department of Dermatology, University of Vienna, Austria.
Klosner
G
G
Pourmojib
M
M
Knobler
R
R
Schwarz
T
T
D015152:Blotting, Northern; D018929:Cell Culture Techniques; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D010431:Pentoxifylline / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D010431:Pentoxifylline