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ALLOGRAFT INFLAMMATORY FACTOR-1 IN ASSOCIATION WITH IL-18 EXPRESSION DETECTED BY MICROARRAY CORRELATES WITH REJECTION AND DEVELOPMENT OF CARDIAC ALLOGRAFT VASCULOPATHY.
Olga D. McDaniel, Ph.D., Sani Z. Yamout, MD, Georgio Aru, MD and Charles K. Moore, MD. Jackson MS, USA, University of MS Medical Center, 39216-4505, Surgery and Medicine.

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Introduction: Coronary vasculopathy (CV) is a major factor in long-term survival of heart transplantation. The emerging evidence suggests that inflammation might be a common background between CV and rejection. Cytokines are strong regulatory molecules that accelerate or inhibit the process of inflammation. Therefore, we hypothesized that an array of cytokine genes might identify differences and might allow early detection of allograft dysfunction. Methods: The PBMCs from allograft recipients with varying degree of CV and/ or grade 3A/3B rejection episodes were tested for their capacity to express cytokines at the mRNA level by using cytokine microarrays. Results: Analysis of the microarray hybridization pattern showed that AIF-1, IFN-α and γ, IL-18, FGFs and TNF-α and β were expressed with a high intensity in the PBMCs of patients with strong CV and patients with grade 3A/3B rejection. In contrast, the AIF-1, TNF-α and FGF-9 were present with less intensity in PBMCs of patient with mild or medium CV, while the IL-18 was minimal. The IL-18 and AIF-1 expression was confirmed by Real time RT-PCR. The calculated relative concentration of AIF-1 was 1.5 times higher than IL-18 expression in patient with strong CV and rejection. Conclusions: Expression level of IL-18 and AIF-1 correlates with severe rejection and CV, thus supporting the role of inflammatory cytokines in posttransplantation events. Rejection episodes of grade 3A/3B correlated with the occurrence of CV in long-term survival of recipients. Such molecular data could provide early detection of the onset of CV and might improve the long-term survival of allograft recipients.