| BackgroundIt is well known that organ transplantation has being gradually accepted as the best treatment for patients who suffered from organ failure. With the amelioration of surgical technique and the use of new immunosuppressants such as Cyclosporin A (CsA) and FK506, the survival of patients who received organ transplantation have been improved. But there are still many patients suffered from graft loss because of allograft rejection and the long-term allograft survival is still frustrated. The acute allograft rejection is thought to be predominantly a T-cell-mediated process which regulated by T cell activator interleukin-2 (IL-2).However, some studies found it became evident that rejection episodes are not always mediated by IL-2. Allograft rejection still occurs in the presence of IL-2/IL-2R blockade. Moreover, IL-2 gene knockout mice and IL-2/IL-4 double-knockout mice are still able to reject allografts. These findings suggest that other cytokines may be involved in these acute EL-2-negative antidonor responses, such as IL-4, IL-7, IL-9, and 1L-15 which can bind to the Y -chain of IL-2 receptor (IL-2R) complex.IL-15 is a recently identified cytokine that is similar hi structure to IL-2 and shares with it a number of biological activities, including its ability to stimulate theproliferation and differentiation of activated T cell and to act as T cell chemotaxis. However, unlike IL-2, IL-15 derive from a wide range of different cell types, including activated macrophages, activated vascular endothelial cells, fibroblasts, muscle cells and epithelial cells. Moreover, although IL-15 and IL-2 share the same IL-2R (3 and common Y -chain receptor subunits, IL-15 use a unique a-chain, IL-15R . .The role of IL-15 in the allograft rejection responses is not clearly defined, but an important role for this cytokine has been suggested in other types of immunopathology, such as inflammatory arthritis, inflammatory bowel disease, sarcoidosis and multiple sclerosis. Some recent studies have observed an increase in the expression of intragraft IL-15 mRNA transcripts in both IL-2-dependent and IL-2-independent allograft rejection and suggested that the increased IL-15 expression correlates with acute rejection. These findings may support the redundancy hypothesis: IL-15 may be a substitute for IL-2 in the rejection process. In order to explore the hypothesis, we investigated the gene expression of IL-15 in transplanted heart in mice and its implication in alloimmune response by means of pathology, RT-PCR and Western-blot. We also explored whether CsA and FK506 were able to inhibit the expression of IL-15 in alloimmune response after heart transplantation in miceMethodsA total of 150 mice (donors and recipients) were used in these experiments. Inbred nale Balb/c (H-2d) mice were used as syngeneic donors and C57BL/6(H-2b) were used as allogeneic donors. All recipients were Balb/c (H-2d) mice who were randomly divided as follows: Group A: Syngeneic control (Balb/c-to-Balb/cy; Group B: Acute rejection (C57BL/6-to-Balb/c); Group C: Acute rejection treated with CsA 10mg/kg/d by intraperitoneal injection from dayO to day13 (C57BL/6-to-Balb/c +CsA). Group D: Acute rejection treated with FK506 1.0mg/kg/d by intraperitoneal injection from dayO to day 13 (C57BL/6-to-Balb/c+FK506). All groups were subdivided into day 1, 3, 5, 7(n=3 each) post-transplantation respectively for sample harvesting, and additional subgroups (n=6 ~ 8) for observation cf general situation and survival time. For observation of general situation and survival time in Group Cand Group F, after 14 days of CsA or FK506 therapy, animals received no additional immunosuppression. Graft specimens were harvested at indicated time to determine morphological changes by pathological examination and the gene expression of IL-15, IL-2 and TNF-a by reverse transcription polymerase chain reaction (RT-PCR). Western-blotting was employed for IL-15, IL-2, TNF- a and IFN- Y proteins expression respectively. All data were expressed as mean SD. Statistical an...
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