Cytokine mRNA expression in chronically rejected human renal allografts

Abstract:  Although both immunologic and non‐immunologic components may cause kidney allograft chronic rejection (KGCR), also referred to as chronic allograft nephropathy (CAN), its pathogenesis is largely not yet understood. To explore relevant immunologic mechanisms occurring in KGCR, we have analyzed in surgically removed KG the transcription of the following cytokine and apoptotic molecule genes: interleukin (IL)‐2, IL‐3, IL‐4, IL‐5, IL‐6, IL‐10, tumor necrosis factor (TNF)‐α, IFN‐γ, FAS, and FAS‐L. Semiquantitative RT‐PCR was used and KG explants were obtained from two groups of transplanted patients. Group 1 was represented by CR/CAN KG, removed for: (a) superimposed symptoms of acute lesions (SAL) due to tapering or suspension of immunosuppression (subgroup 1a, eight cases); (b) causes other than SAL (two cases, subgroup 1b). Group 2 comprised explanted kidneys with no CR/CAN (three cases – vascular thrombosis, intrarenal hemorrhage and vascular thrombosis). The results showed that in group 1 IL‐ 6 was detectable in seven of 10, IL‐10 in six of 10, IFN‐γ in five of 10, and IL‐3 in four of 10 cases with a variable pattern of reciprocal association. IL‐2 and TNF‐α were represented in one of 10 cases only. Particularly, in the subgroup 1b IL‐10 was never detected. Among the most represented cytokines of group 1, IL‐10 as well as IL‐3 were never found in group 2. The peculiar expression of IL‐10 and IL‐3 and partially IL‐6 seems to support the hypothesis that a Th2 pattern predominantly characterizes KGCR, thus indicating that Th2 cytokines, likely produced by different intragraft cell types including T cells, macrophages and natural killer (NK) cells, may represent an important component in the pathogenesis of this process. Moreover, IL‐10 seems to exquisitely characterize a group of CR/CAN kidney grafts more prone to immunologic assaults.