title: Treatment with interleukin-12/23p40 antibody attenuates acute cardiac allograft rejection.
abstract: BACKGROUND
  Interleukin (IL)-12 and -23 share the p40 subunit and are crucial for the development of T helper (Th) 1- and Th17-cell responses in acute graft rejection. However, little is known about the impact of treatment with antagonistic anti-p40 antibody in inhibiting rejection of cardiac allografts.
  
  
  METHODS
  C57BL/6 mice were transplanted with syngeneic or allogeneic (BALB/c) hearts and treated with 100 or 200 μg or 400 μg anti-P40 monoclonal antibody on postoperative days 1 and 3, respectively. The survival of grafts was monitored daily by abdominal palpation until the complete cessation of cardiac contractility (endpoint). The severity of acute rejection was evaluated by histology and immunohistochemistry. The expression of transcription factors within the grafts were measured by quantitative real-time polymerase chain reaction. Systemically, the lymphocytes were characterized by flow cytometry, and the serum levels of cytokines were determined by ELISA.
  
  
  RESULTS
  In comparison with mice treated with isotype IgG or saline, treatment with anti-p40 significantly alleviated acute phase allograft rejection and resulted in prolonged survival of cardiac allografts (P<0.05). These changes were associated with reduced infiltration of inflammatory cells and down-regulation of Th1- and Th17-specific transcription factors and cytokines. Furthermore, treatment with anti-p40 significantly reduced the percentages of splenic Th1 and Th17 cells, but not Th2 and regulatory T cells (P<0.05), with concomitant reduction of serum interferon-γ and IL-17 levels (P<0.05).
  
  
  CONCLUSIONS
  Our data indicated that treatment with anti-p40 inhibited Th1- and Th17-cell responses and prolonged the survival of cardiac allografts in mice.
authors: Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China.
authors: Aini
authors: A
authors: Xie
authors: Sihua
authors: S
authors: Wang
authors: Kailun
authors: K
authors: Zhang
authors: Guohua
authors: G
authors: Wang
authors: Ping
authors: P
authors: Ye
authors: Jun
authors: J
authors: Li
authors: Wenhao
authors: W
authors: Chen
authors: Jiahong
authors: J
authors: Xia
mesh_terms: D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D006084:Graft Rejection / Q000628:therapy*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D053762:Interleukin-12 Subunit p40 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D014157:Transcription Factors