Details

Autor(en) / Beteiligte

• Dudler, Jean
• Simeoni, Eleonora
• Fleury, Sylvain
• Li, Jianping
• Pagnotta, Maria
• Pascual, Manuel
• Von Segesser, Ludwig K.
• Vassalli, Giuseppe

Titel

Gene transfer of interleukin‐18‐binding protein attenuates cardiac allograft rejection

Ist Teil von

• Transplant international, 2007-05, Vol.20 (5), p.460-466

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2007

Quelle

Wiley

Beschreibungen/Notizen

• Summary Interleukin (IL) 18 is a potent pro‐inflammatory Th1 cytokine that exerts pleiotropic effector functions in both innate and acquired immune responses. Increased IL‐18 production during acute rejection has been reported in experimental heart transplantation models and in kidney transplant recipients. IL‐18‐binding protein (IL‐18BP) binds IL‐18 with high affinity and neutralizes its biologic activity. We have analyzed the efficacy of an adenoviral vector expressing an IL‐18BP‐Ig fusion protein in a rat model of heart transplantation. IL‐18BP‐Ig gene transfer into Fisher (F344) rat donor hearts resulted in prolonged graft survival in Lewis recipients (15.8 ± 1.4 days vs. 10.3 ± 2.5 and 10.1 ± 2.1 days with control virus and buffer solution alone, respectively; P < 0.001). Immunohistochemical analysis revealed decreased intra‐graft infiltrates of monocytes/macrophages, CD4+, CD8α+ and T‐cell receptor αβ+ cells after IL‐18BP‐Ig versus mock gene transfer (P < 0.05). Real‐time reverse transcriptase polymerase chain reaction analysis showed decreased cytokine transcripts for the RANTES chemokine and transforming growth factor‐β after IL‐18BP‐Ig gene transfer (P < 0.05). IL‐18BP‐Ig gene transfer attenuates inflammatory cell infiltrates and prolongs cardiac allograft survival in rats. These results suggest a contributory role for IL‐18 in acute rejection. Further studies aiming at defining the therapeutic potential of IL‐18BP are warranted.