Interleukin-2 nephrotoxicity assessed in vitro.
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.
Hall
T J
TJ
MD Laboratories, Congleton, Cheshire, U.K.
James
P R
PR
Cambridge
G
G
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D007376:Interleukin-2 / Q000009:adverse effects* / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced*; D013552:Swine; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D007376:Interleukin-2; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; C022616:thiazolyl blue