PMID- 9172017 OWN - NLM STAT- MEDLINE DCOM- 19970818 LR - 20190909 IS - 0192-0561 (Print) IS - 0192-0561 (Linking) VI - 18 IP - 12 DP - 1996 Dec TI - Differential regulation of TNF alpha, IL-1 beta, IL-6, IL-8, TNF beta, and IL-10 by pentoxifylline. PG - 739-48 AB - Pentoxifylline (PTX) is a methylxanthine drug known to inhibit the production of tumor necrosis factor-alpha (TNF alpha), which plays a key role in inflammation. Recent studies also revealed that other cytokines may be inhibited by PTX. We investigated PTX effects on production and mRNA expression of TNF alpha, IL-1 beta, IL-6, IL-8, TNF beta and IL-10. Cytokine release was studied in 1/10 diluted whole blood culture (WB) and in peripheral blood mononuclear cell (PBMC) culture. Cytokine production was triggered in both culture systems by endotoxin (LPS) or by phorbol ester (PMA) plus phytohemagglutinin (PHA). Our results showed that expression and production of TNF alpha and TNF beta were inhibited by PTX in a dose-dependent manner. Moreover, we observed that depending on the way of activating cells, PTX induced an up- or a down-regulation (in PMA + PHA or LPS stimulated cells, respectively) for IL-1 and IL-6 release. We also noted that the effects of PTX on IL-6, IL-8 and IL-10 production were different in WB and in PBMC culture. In conclusion PTX acts on cytokine in a complex manner depending on cellular environment and on the method of activation. FAU - D'Hellencourt, C L AU - D'Hellencourt CL AD - Laboratoire d'Hematologie, C.H.R. Robert Debre, Reims, France. Hellenco@angers.inserm.fr FAU - Diaw, L AU - Diaw L FAU - Cornillet, P AU - Cornillet P FAU - Guenounou, M AU - Guenounou M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Int J Immunopharmacol JT - International journal of immunopharmacology JID - 7904799 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (Lipopolysaccharides) RN - 0 (Lymphotoxin-alpha) RN - 0 (Phytohemagglutinins) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vasodilator Agents) RN - 130068-27-8 (Interleukin-10) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - SD6QCT3TSU (Pentoxifylline) SB - IM MH - Anti-Inflammatory Agents/pharmacology MH - Cytokines/biosynthesis/drug effects/genetics MH - Down-Regulation/drug effects MH - Gene Expression MH - Gene Expression Regulation MH - Humans MH - Interleukin-1/*antagonists & inhibitors/*genetics MH - Interleukin-10/*antagonists & inhibitors/*genetics MH - Interleukin-6/*antagonists & inhibitors/*genetics MH - Interleukin-8/*antagonists & inhibitors/*genetics MH - Leukocytes, Mononuclear/metabolism MH - Lipopolysaccharides/pharmacology MH - Lymphotoxin-alpha/*antagonists & inhibitors/*genetics MH - Pentoxifylline/*pharmacology MH - Phytohemagglutinins/pharmacology MH - RNA, Messenger/metabolism MH - Tetradecanoylphorbol Acetate/pharmacology MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/*genetics MH - Vasodilator Agents/*pharmacology EDAT- 1996/12/01 00:00 MHDA- 1996/12/01 00:01 CRDT- 1996/12/01 00:00 PHST- 1996/12/01 00:00 [pubmed] PHST- 1996/12/01 00:01 [medline] PHST- 1996/12/01 00:00 [entrez] AID - S0192056197855567 [pii] AID - 10.1016/s0192-0561(97)85556-7 [doi] PST - ppublish SO - Int J Immunopharmacol. 1996 Dec;18(12):739-48. doi: 10.1016/s0192-0561(97)85556-7.