title: Effects of kirenol on bovine type II collagen-induced rat lymphocytes in vivo and in vitro.
abstract: OBJECTIVE
  To investigate the effect of kirenol on bovine type II collagen (CII)-specific lymphocytes in vivo and in vitro, and explore the mechanism of kirenol-induced immunosuppression in antigen-specific lymphocytes.
  
  
  METHODS
  Twenty-four Wistar rats were randomized into control group, collagen-induced arthritis (CIA) model group, kirenol group (2 mg/kg), and prednisolone group (2 mg/kg). After CII injection, the rats in the latter two groups received intragastric administration of kirenol and prednisolone for 30 days, and the spleens and draining lymph nodes of the rats were harvested to prepare single cell suspensions for measurement of the cytokine levels using ELISA. In the in vitro experiment, the lymphocytes from the control rats, with or without 20 µg/ml CII treatment in the presence of 0-80 µg/ml kirenol, were evaluated for cell proliferation and apoptosis using [(3)H]-thymidine incorporation and flow cytometry, respectively.
  
  
  RESULTS
  Compared with those in CIA group, IFN-γ and TNF-α production was significantly reduced in splenocyte culture supernatant of kirenol group (P<0.05 and P<0.01, respectively), and the level of IL-10 and IL-4 was up-regulated (P<0.05 and P<0.01, respectively); IFN-γ and TNF-α secretion by the cultured lymph node cells (LNCs) significantly decreased (P<0.05 and P<0.001, respectively) and IL-10 and IL-4 production increased (P<0.05, P<0.001) in kirenol group. In the in vitro experiment, kirenol treatment caused obvious suppression of CII-induced LNC proliferation and dose-dependently induced antigen-specific apoptosis of the splenocytes and LNCs.
  
  
  CONCLUSIONS
  Kirenol treatment reduces pro-inflammatory cytokine secretion, increases anti-inflammatory cytokine production, inhibits  cell proliferation and induces apoptosis of CII-specific lymphocytes in vitro, suggesting the potential of kirenol as an immunosuppressant.
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Juan
authors.initials: J
authors.lastname: Xiao
authors.forename: Zaiwang
authors.initials: Z
authors.lastname: Wu
authors.forename: Zheming
authors.initials: Z
authors.lastname: Wang
authors.forename: Hongzheng
authors.initials: H
authors.lastname: Fu
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Qian
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D016207:Cytokines; D004224:Diterpenes; D007166:Immunosuppressive Agents; C560087:kirenol