Pentoxifylline inhibits perforin-dependent natural cytotoxicity in vitro.
Pentoxifylline (PTX) is commonly used in peripheral blood vessel diseases, however it has also been found to decrease the level of proinflammatory cytokines such as IL-12, TNF-alpha and IFN-gamma. Moreover, some authors reported that PTX suppresses spontaneous cytotoxicity of peripheral blood mononuclear cells (PBMC) in vitro. It could influence the mechanism of killing target cells by PBMC. For this reason we evaluated the influence of PTX on spontaneous cytotoxicity of PBMC against K562 and CaSki cell lines. Subsequently, we compared this effect to that evoked by dexamethasone, one of the most effective anti-inflammatory drugs. Our study revealed that PTX inhibits natural cytotoxicity preferentially through inhibition of perforin-mediated cell membrane damage, without a statistically significant influence on apoptosis induction. Furthermore, pentoxifylline inhibits natural cytotoxicity as effectively as dexamethasone. However, the result of PTX inhibitory influence is observed much earlier than that of dexamethasone. Currently PTX is commonly used in diseases that occur more frequently in elderly patients. We suggest that PTX, inhibiting perforin-dependent PBMC cytotoxic activity, could weaken anti-cancer action of immune system thus accelerating the progress of neoplasm formation in these patients.
Lazarczyk
M
M
Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, Warsaw, Poland.
Grzela
T
T
Korczak-Kowalska
G
G
Niderla
J
J
Oldak
M
M
Jozwiak
J
J
Skopinski
P
P
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D002857:Chromium / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000235:genetics; D012878:Skin Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D002857:Chromium; D054353:Perforin; D003907:Dexamethasone; D010431:Pentoxifylline