title: Expression of tumor necrosis factor-alpha, interleukin-6, and interferon-gamma in spontaneous chronic pancreatitis in the WBN/Kob rat.
abstract: To clarify the pathophysiological significance of cytokines in chronic pancreatitis (CP), we analyzed tissue expressions of various cytokines in the onset and progression of spontaneous CP in the WBN/Kob rat. Four-week-old male WBN/Kob rats were fed a special pellet diet (MB-3) for 20 weeks, and 6 rats were killed every 4 weeks. Pathologically, CP occurred at 12 weeks and progressed thereafter. The inflammation and fibrosis peaked at 12 and 16 weeks, respectively. By semiquantitative reverse transcription-polymerase chain reaction, the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and interferon (IFN)-gamma mRNAs peaked at 8, 12, and 16 weeks, respectively. Immunohistochemistry showed IL-6 expression in infiltrating inflammatory cells and vascular endothelial cells, whereas TNF-alpha was expressed in both acinar and infiltrating cells. IFN-gamma was localized to acinar, infiltrating and ductal cells, and its expression intensity showed significant correlation with those of fibrosis, type III collagen and alpha-smooth muscle actin. The in situ hybridization results were consistent with the RT-PCR data. These results suggest that tissue expressions of TNF-alpha and IL-6 are involved in the onset of pancreatitis and that IFN-gamma expression is related to the progression of CP.
authors.affiliation: Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University, Japan.
authors.forename: M J
authors.initials: MJ
authors.lastname: Xie
authors.forename: Y
authors.initials: Y
authors.lastname: Motoo
authors.forename: S B
authors.initials: SB
authors.lastname: Su
authors.forename: N
authors.initials: N
authors.lastname: Sawabu
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000235:genetics; D005355:Fibrosis; D015870:Gene Expression; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000199:Actins; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003094:Collagen