While a wide range of factors contributes to allograft survivability, routine screening of cytokine gene polymorphisms may have important clinical relevance and therefore should be considered in the design of both pre- and post-treatment regimens. Most cytokines have been demonstrated to be transcriptionally controlled. Cytokines influence the local activation of cells and play a critical role in the regulation of immune responses. While functional affects have been attributed to cytokine gene variants (Hoffmann et al., 2001; Louis et al., 1998; Turner et al., 1997), their role in allograft rejection remains controversial. The level of production of many of these cytokines may be important in accelerating or slowing the rejection process. The inheritance of genetically determined polymorphisms has been implicated in the development of both acute and chronic renal allograft rejection (Hutchinson, 1999; Hutchinson et al., 2000) and peripheral tolerance (Burlingham et al., 2000). Indeed, some studies have shown allelic variations within cytokine genes might act on the microenvironment of responding T cells and APCs, and thereby regulate allograft survival. A more clear definition of cytokine genotypes may indicate how recipients will respond to their transplants and guide both optimal immunotherapy, organ selection, or enable selection of patient subgroups for individualized clinical trials (Hoffmann et al., 2001, Sankaran et al., 1999).
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