title: Interleukin-16 deficiency suppresses the development of chronic rejection in murine cardiac transplantation model.
abstract: BACKGROUND
  IL-16 promotes the recruitment of various cells expressing CD4, a receptor for IL-16. The precise role of IL-16 in transplant rejection remains unknown; therefore, the present study investigated the contribution of IL-16 to the development of chronic rejection in heart transplants.
  
  
  METHODS
  C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into (1) IL-16-deficient (IL-16(-/-)) C57BL/6J or (b) wild type (WT) control recipients (MHC class II mismatch). Grafts were harvested at 52 days, parenchymal rejection was assessed by the ISHLT grading system, and CAV was examined morphometrically. Graft infiltrating cells were detected 10 and 52 days after transplantation. Intragraft cytokine and chemokine profiles were assessed. To confirm the role of IL-16 in CAV development, C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into C57BL/6J WT recipients treated with (1) anti-IL-16-neutralization monoclonal antibody or (b) control immunoglobulin G. Grafts were harvested at 52 days, and CAV was quantified morphometrically. Graft-infiltrating cells were examined histologically.
  
  
  RESULTS
  Parenchymal rejection and CAV was significantly attenuated in donor hearts transplanted into IL-16(-/-) recipient mice compared with WT controls. Donor hearts transplanted into IL-16(-/-) recipients had a significant reduction in coronary artery luminal occlusion, intima-to-media ratio, and percentage of diseased vessels. CAV was associated with decreased donor organ inflammation, as well as donor organ cytokine (IL-1β and IL-6) and chemokine (MCP-1 and KC) protein expression. Intimal proliferation and inflammatory cell infiltration were significantly reduced in hearts transplanted into recipients treated with an IL-16-neutralization antibody.
  
  
  CONCLUSIONS
  IL-16-deficiency reduced graft inflammatory cell recruitment, and allograft inflammatory cytokine and chemokine production. Therefore, IL-16 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection.
authors: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California 94305, USA.
authors: Naoyuki
authors: N
authors: Kimura
authors: Satoshi
authors: S
authors: Itoh
authors: Susumu
authors: S
authors: Nakae
authors: Robert C
authors: RC
authors: Axtell
authors: Jeffrey B
authors: JB
authors: Velotta
authors: Ernst Jan
authors: EJ
authors: Bos
authors: Denis R
authors: DR
authors: Merk
authors: Yongquan
authors: Y
authors: Gong
authors: Homare
authors: H
authors: Okamura
authors: Claude M
authors: CM
authors: Nagamine
authors: Hideo
authors: H
authors: Adachi
authors: Hardy
authors: H
authors: Kornfeld
authors: Robert C
authors: RC
authors: Robbins
authors: Michael P
authors: MP
authors: Fischbein
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications / Q000503:physiopathology* / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D016027:Heart Transplantation / Q000502:physiology*; D019410:Interleukin-16 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects
chemical_list: D000906:Antibodies; D018925:Chemokines; D016207:Cytokines; D019410:Interleukin-16