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Interleukin-2 nephrotoxicity assessed in vitro
T J Hall1, P R James, G Cambridge
1MD Laboratories, Congleton, Cheshire, U.K.
Immunotherapy with interleukin-2 (IL-2) is complicated by many side effects of which nephrotoxicity is the most limiting. We have examined IL-2 nephrotoxicity in vitro using the pig kidney cell line LLC-PK.1 model system. Human recombinant IL-2 (HrIL-2) was toxic to LLC-PK.1 cells at concentrations comparable to those seen in the serum of patients undergoing cancer immunotherapy. Many of the side effects of IL-2 immunotherapy are due to IL-2-induced synthesis of tumour necrosis factor-alpha (TNF-a) and can be alleviated by co-administration of steroids. However, HrIL-2 nephrotoxicity in vitro was unaffected by addition of dexamethasone to cultures and LLC-PK.1 cells were found to be resistant to the anti-proliferative effects of TNF-a. These results suggest that the nephrotoxic effect of HrIL-2 is due to a direct toxic effect on kidney cells.
Immunotherapy with interleukin-2 (IL-2) is complicated by many side effects of which nephrotoxicity is the most limiting. We have examined IL-2 nephrotoxicity in vitro using the pig kidney cell line LLC-PK.1 model system. Human recombinant IL-2 (HrIL-2) was toxic to LLC-PK.1 cells at concentrations comparable to those seen in the serum of patients undergoing cancer immunotherapy. Many of the side effects of IL-2 immunotherapy are due to IL-2-induced synthesis of tumour necrosis factor-alpha (TNF-a) and can be alleviated by co-administration of steroids. However, HrIL-2 nephrotoxicity in vitro was unaffected by addition of dexamethasone to cultures and LLC-PK.1 cells were found to be resistant to the anti-proliferative effects of TNF-a. These results suggest that the nephrotoxic effect of HrIL-2 is due to a direct toxic effect on kidney cells.