PMID- 15648785 OWN - NLM STAT- MEDLINE DCOM- 20050428 LR - 20131121 IS - 0091-7370 (Print) IS - 0091-7370 (Linking) VI - 34 IP - 4 DP - 2004 Autumn TI - Pentoxifylline inhibits endotoxin-induced NF-kappa B activation and associated production of proinflammatory cytokines. PG - 427-36 AB - The effects of graded doses of pentoxifylline (PTX) on endotoxin-induced production of inflammatory cytokines and activation of nuclear factor kappa B (NF-kappaB) were studied in vivo in rat intestine. Sepsis was induced in rats by ip injection of lipopolysaccharide (LPS, 5 mg/kg). PTX was injected via the tail vein at dosages of 6.25, 12.5, 25, 50, or 100 mg/kg at 1 min after LPS challenge. NF-kappaB activation in intestine was investigated by electrophoretic mobility shift assay (EMSA). Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels were measured in intestine by enzyme-linked immunosorbance assays (ELISA). Intestinal TNF-alpha, IL-6, and IL-10 mRNA expression were studied by the reverse-transcription polymerase chain reaction (RT-PCR). The measurements of NF-kappaB, TNF-alpha, IL-6, and IL-10 were performed, respectively, at 1, 4, 4, and 1 hr after endotoxin injection. The results showed that LPS elevated the production of TNF-alpha, IL-6, and IL-10 and enhanced NF-kappaB activation in rat intestine. At all dosages, PTX reduced the activation of NF-kappaB and the production of TNF-alpha and IL-6, but enhanced the release of IL-10. These effects were greatest at dosages of 50 mg/kg for TNF-alpha and IL-6, and 25 mg/kg for IL-10. In conclusion, PTX suppressed the production of proinflammatory cytokines such as TNF-alpha and IL-6 in rat intestine, and enhanced the endotoxin-induced production of IL-10. The suppressive effect of proinflammatory cytokines may act by inhibiting NF-kappaB activation, but not by induction of IL-10. FAU - Ji, Qing AU - Ji Q AD - Department of Anesthesiology, Jinling Hospital, Nanjing, People's Republic of China. FAU - Zhang, Lidong AU - Zhang L FAU - Jia, Hongbin AU - Jia H FAU - Xu, Jianguo AU - Xu J LA - eng PT - Journal Article PL - United States TA - Ann Clin Lab Sci JT - Annals of clinical and laboratory science JID - 0410247 RN - 0 (Cytokines) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vasodilator Agents) RN - 130068-27-8 (Interleukin-10) RN - SD6QCT3TSU (Pentoxifylline) SB - IM MH - Animals MH - Cytokines/*biosynthesis/genetics MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Drug Therapy, Combination MH - Endotoxemia/*metabolism/pathology MH - Enzyme-Linked Immunosorbent Assay MH - Injections, Intravenous MH - Interleukin-10/biosynthesis/genetics MH - Interleukin-6/biosynthesis/genetics MH - Jejunum/*drug effects/metabolism MH - Lipopolysaccharides/pharmacology MH - Male MH - NF-kappa B/*antagonists & inhibitors/biosynthesis MH - Pentoxifylline/administration & dosage/*pharmacology MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Wistar MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/biosynthesis/genetics MH - Vasodilator Agents/administration & dosage/*pharmacology EDAT- 2005/01/15 09:00 MHDA- 2005/04/29 09:00 CRDT- 2005/01/15 09:00 PHST- 2005/01/15 09:00 [pubmed] PHST- 2005/04/29 09:00 [medline] PHST- 2005/01/15 09:00 [entrez] PST - ppublish SO - Ann Clin Lab Sci. 2004 Autumn;34(4):427-36.