A patient with renal cell cancer developed acute renal failure due to biopsy-proven acute tubulo-interstitial nephritis (AIN) in the 6th week of continuous infusion of 9 × 106 IU m−2 day−1 recombinant interleukin-2 (rIL-2). We investigated whether the AIN was the result of a cellular cytotoxic reaction induced by the rIL-2 treatment. The cytolytic activity of cryopreserved peripheral blood lymphocytes (PBL), isolated before and at the end of the rIL-2 treatment (at the time of AIN), was studied after 5 days of culture with or without rIL-2 or anti-CD28 and immobilized anti-CD3 antibodies. The PBL isolated before and at the end of the rIL-2 treatment showed cytolytic activity towards a number of allogeneic targets. However, only the PBL isolated at the end of the rIL-2 treatment showed, when stimulated with rIL-2 in vitro, significant cytolytic activity against an autologous renal cell line cultured from the AIN biopsy specimen and against an allogeneic renal cell cancer cell line. These PBL displayed no enhanced killing capacity towards autologous PBL and the melanoma cell line M14. These observations suggest that the AIN may be the result of a cytotoxic lymphocyte-mediated reaction induced by the rIL-2 treatment.
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Averbuch SD, Austin III HA, Sherwin SA, Antonovych T, Bunn PA, Longo DL (1984) Acute interstitial nephritis with the nephrotic syndrome following recombinant leukocyte A interferon therapy for mycosis fungoides. N Engl J Med 310: 32
Bastuji-Garin S, Chosidow O, Lang P, Roujeau J-C, Revuz J (1990) Transient proteinuria during interleukin-2 therapy. Eur J Cancer 26: 924
Beaufils H, Patte R, Aubert Ph, Camey M, Kuss R, Barbagelatta M, Chomette G (1984) Renal Immunopathology in renal cell carcinoma. Virchows Arch [A] 404: 87
Belldegrun A, Webb DE, Austin III HA, Steinberg SM, White DE, Linehan WM, Rosenberg SA (1987) Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer. Ann Intern Med 106: 817
Bender JR, Pardi R, Engleman E (1990) T-cell receptor-negative natural killer cells display antigen-specific cytotoxicity for microvascular endothelial cells. Proc Natl Acad Sci USA 87: 6949
Bolhuis RLH, Stoter G, Eggermont AMM. Characteristics and uses of IL-2 in immunotherapy. Biotherapy 1989: 1–153
Cameron JS (1988) Allergic interstitial nephritis: clinical features and pathogenesis. Q J Med 250: 97
Diekman MJM, Vlasveld LT, Krediet RT, Rankin EM, Arisz L (1992) Acute interstitial nephritis during continuous intravenous administration of low-dose interleukin-2. Nephron 60: 122
Ebert T, Bander NH (1990) Immunodiagnosis of renal cell carcinoma. In: Herberman RB, Mercer DW (eds) Immunodiagnosis of cancer. Dekker, New York, p 469
Feinfeld DA, D'Agati V, Dutcher JP, Werfel SB, Lynn RI, Wiernik PH (1991) Interstitial nephritis in a patient receiving adoptive immunotherapy with recombinant interleukin-2 and lymphokine-activated killer cells. Am J Nephrol 11: 489
Fer MF, McKinney TD, Richardson RL, Hande KR, Oldham RK, Greco FA (1981) Cancer and the kidney: renal complication of neoplasms. Am J Med 71: 704
Hank JA, Kohler PC, Weil-Hillman G, Rosenthal N, Moore KH, Storer B, Minkoff D, Bradshaw J, Bechhofer R, Sondel PM (1988) In vivo induction of the lymphokine-activated killer phenomenon: interleukin-2-dependent human non-major histocompatibility complex-restricted cytotoxicity generated in vivo during administration of human recombinant interleukin-2. Cancer Res 48: 1965
Kelly CJ, Korngold R, Mann R, Clayman M, Haverty T, Neilson EG, (1986) Spontaneous interstitial nephritis in kdkd mice: II. Characteriziation of a tubular antigen-specific, H-2K-restricted Lyt-2+ effector T cell that mediates destructive tubulointerstitial injury. J Immunol 136: 526
Kerpen HO, Bhat JG, Feiner HD, Baldwin DS (1978) Membranous nephropathy associated with renal cell carcinoma: evidence against a role of renal tubular or tumor antibodies in pathogenesis. Am J Med 64: 863
Koo AS, Tso C-L, Shimabukuro T, Peyret C, deKernion JB, Belldegrun A (1991) Autologous tumor-specific cytotoxicity of tumor-infiltrating lymphocytes derived from human renal cell carcinoma. J Immunother 10: 347
Kragel AH, Travis WD, Feinberg L, Pittaluga S, Striker LM, Roberts WC, Lotze MT, Yang JJ, Rosenberg SA (1990) Pathological findings associated with interleukin-2 based immunotherapy for cancer: a postmortem study of 19 patients. Hum Pathol 21: 493
Kroemer G, Andreu JL, Gonzalo JA, Gutierrez-Ramos JC, Martinez-AC (1991) Interleukin-2, autotolerance, and autoimmunity. Adv Immunol 50: 147
Krutchik An, Buzdar AU, Akhtar M, Blumenschein GR (1980) Immune-complex glomerulonephritis secondary to nonspecific immunotherapy. Cancer 45: 495
Miltenburg AMM, Meijer-Paape ME, Daha MR, Paul LC (1988) Lymphokine-activated killer cells lyse human renal cancer lines and cultured normal kidney cells. Immunology 63: 729
Neilson EG (1989) Pathogenesis and therapy of interstitial nephritis. Kidney Int 35: 1257
Nijhuis EWP, v/d Wiel-van Kemenade E, Figdor CG, van Lier RAW (1990) Activation and expansion of tumour-infiltrating lymphocytes by anti-CD3 and anti-CD28 monoclonal antibodies. Cancer Immunol Immunother 32: 245
Oosterwijk E, Ruiter DJ, Wakka JC, Huiskens-v d Mey JW, Jonas U, Fleuren GJ, Zwartendijk J, Hoedemaeker Ph, Warnaar SO (1986) Immunohistochemical analysis of monoclonal antibodies to renal antigens. Application in the diagnosis of renal cell carcinoma. Am J Pathol 123: 301
Oosterwijk E, Ruiter DJ, Hoedemaeker PhJ, Pauwels EKJ, Jonas U, Zwartendijk J, Warnaar SO (1986) Monoclonal antibody G250 recognizes a determinant present in renal-cell carcinoma and absent from normal kidney. Int J Cancer 38: 489
Oshimi K, Oshimi Y, Saito H, Mizoguchi H (1988) Cytotoxicity of interleukin-2-activated lymphocytes for autologous normal blood mononuclear cells. J Immunol Methods 109: 161
Shalmi CL, Dutcher JP, Feinfeld DA, Chun KJ, Saleemi K, Freeman LM, Lynn RI, Wiernik PH (1990) Acute renal dysfunction during interleukin-2 treatment: suggestion of an intrinsic renal lesion. J Clin Oncol 8: 1839
Textor SC, Margolin K, Blayney D, Carlson J, Doroshow J (1987) Renal, volume, and hormonal changes during therapeutic administration of recombinant interleukin-2 in man. Am J Med 83: 1055
Vlasveld LT, Rankin EM, Hekman A, Rodenhuis S, Beijnen JH, Hilton AM, Dubbelman AC, Vyth-Dreese FA, Melief CJM (1992) A phase I study of prolonged continuous infusion of low dose recombinant interleukin-2 in melanoma and renal cell cancer: part I. Clinical aspects. Br J Cancer 65: 744
Wang J, Walle A, Gordon B, Novogrodsky A, Suthanthiran M, Rubin AL, Morrison H, Silver RT, Stenzel KH (1987) Adoptive immunotherapy for stage IV renal cell carcinoma: a novel protocol utilizing periodate and interleukin-2-activated autologous leukocytes and continuous infusions of low-dose interleukin-2. Am J Med 83: 1016
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Vlasveld, L.T., van de Wiel-van Kemenade, E., de Boer, A.J. et al. Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer. Cancer Immunol Immunother 36, 210–213 (1993). https://doi.org/10.1007/BF01741094
- Acute interstitial nephritis
- Renal cell cancer