In vitro immunomodulatory effects of pentoxifylline.
Pentoxifylline (PTX), a methylxanthine derivative and phosphodiesterase inhibitor, is known to influence production and/or function of some cytokines. We examined the effect of PTX on the in vitro expression of cytokine genes using endotoxin- or phytohaemagglutinin (PHA)-stimulated human blood mononuclear cells. The expression of tumour necrosis factor (TNF)alpha, TNF beta interleukin (IL)-2 and interferon (IFN)gamma was inhibited by PTX in a dose-dependent manner, whereas expression of IL-1 alpha, IL-1 beta, and IL-6 was unaffected at concentrations up to 300 microM of PTX. The amount of TNF beta mRNA in PHA-stimulated blood mononuclear cells was reduced by PTX. Finally, PTX stimulated PHA-induced cell proliferation whereas antigen-induced cell proliferation was inhibited in the presence of PTX. The PTX analogues HWA-138 and A-802715 inhibited TNF alpha mRNA expression from endotoxin-stimulated mononuclear cells. These data suggest that PTX-analogues affect the in vitro immune response at different target points and that the response depends upon the respective triggering mechanism(s).
Rieneck
K
K
Laboratory of Medical Immunology 7544, Rigshospitalet, Copenhagen, Denmark.
Diamant
M
M
Haahr
P M
PM
Schönharting
M
M
Bendtzen
K
K
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D004731:Endotoxins; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009693:Nucleic Acid Hybridization; D010431:Pentoxifylline / Q000494:pharmacology*; D010835:Phytohemagglutinins; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D016207:Cytokines; D004731:Endotoxins; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D012313:RNA; D010431:Pentoxifylline