Abstract
Rats receiving a single dose (10 mg/100 g) of aminonucleoside of puromycin (PAN) develop heavy proteinuria and acute interstitial nephritis (AIN). Whole isolated glomeruli from rats injected with PAN secreted both TNF-alpha and IL-1 beta cytokines. TNF-alpha secretion was first and maximally detected on day 3, whereas IL-beta activity was found on day 7, when rats were heavily proteinuric and AIN developed. In vivo treatment with either anti-TNF-alpha or anti-IL-1 beta antibodies produced a drastic and simultaneous reduction in both levels of proteinuria and intensity of interstitial cell infiltrate. These effects improved when both antibodies were administered together. Our studies demonstrate the effectiveness of immunosuppressive therapy against these two cytokines in rats with PAN-induced nephrosis.
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bricio T., Molina A., Egido J., Gonzalez E., Mampaso F. IL-1-like production in adriamycin-induced nephrotic syndrome in the rat. Clin Exp Immunol. 1992 Jan;87(1):117–121. doi: 10.1111/j.1365-2249.1992.tb06423.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burlington H., Cronkite E. P. Characteristics of cell cultures derived from renal glomeruli. Proc Soc Exp Biol Med. 1973 Jan;142(1):143–149. doi: 10.3181/00379727-142-36977. [DOI] [PubMed] [Google Scholar]
- Camussi G., Bussolino F., Salvidio G., Baglioni C. Tumor necrosis factor/cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet-activating factor. J Exp Med. 1987 Nov 1;166(5):1390–1404. doi: 10.1084/jem.166.5.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
- Cotran R. S., Pober J. S. Effects of cytokines on vascular endothelium: their role in vascular and immune injury. Kidney Int. 1989 Apr;35(4):969–975. doi: 10.1038/ki.1989.80. [DOI] [PubMed] [Google Scholar]
- Diamond J. R. Effects of dietary interventions on glomerular pathophysiology. Am J Physiol. 1990 Jan;258(1 Pt 2):F1–F8. doi: 10.1152/ajprenal.1990.258.1.F1. [DOI] [PubMed] [Google Scholar]
- Diamond J. R., Karnovsky M. J. Focal and segmental glomerulosclerosis following a single intravenous dose of puromycin aminonucleoside. Am J Pathol. 1986 Mar;122(3):481–487. [PMC free article] [PubMed] [Google Scholar]
- Diamond J. R., Pesek I. Glomerular tumor necrosis factor and interleukin 1 during acute aminonucleoside nephrosis. An immunohistochemical study. Lab Invest. 1991 Jan;64(1):21–28. [PubMed] [Google Scholar]
- Diamond J. R., Pesek I., Ruggieri S., Karnovsky M. J. Essential fatty acid deficiency during acute puromycin nephrosis ameliorates late renal injury. Am J Physiol. 1989 Nov;257(5 Pt 2):F798–F807. doi: 10.1152/ajprenal.1989.257.5.F798. [DOI] [PubMed] [Google Scholar]
- Eddy A. A., Crary G. S., Michael A. F. Identification of lymphohemopoietic cells in the kidneys of normal rats. Am J Pathol. 1986 Aug;124(2):335–342. [PMC free article] [PubMed] [Google Scholar]
- Eddy A. A., McCulloch L., Liu E., Adams J. A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. Am J Pathol. 1991 May;138(5):1111–1123. [PMC free article] [PubMed] [Google Scholar]
- Eddy A. A., Michael A. F. Acute tubulointerstitial nephritis associated with aminonucleoside nephrosis. Kidney Int. 1988 Jan;33(1):14–23. doi: 10.1038/ki.1988.3. [DOI] [PubMed] [Google Scholar]
- FRENK S., ANTONOWICZ I., CRAIG J. M., METCOFF J. Experimental nephrotic syndrome induced in rats by aminonucleoside; renal lesions and body electrolyte composition. Proc Soc Exp Biol Med. 1955 Jul;89(3):424–427. doi: 10.3181/00379727-89-21833. [DOI] [PubMed] [Google Scholar]
- Harris K. P., Lefkowith J. B., Klahr S., Schreiner G. F. Essential fatty acid deficiency ameliorates acute renal dysfunction in the rat after the administration of the aminonucleoside of puromycin. J Clin Invest. 1990 Oct;86(4):1115–1123. doi: 10.1172/JCI114816. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ikuta S., Kirby J. A., Shenton B. K., Givan A. L., Lennard T. W. Human endothelial cells: effect of TNF-alpha on peripheral blood mononuclear cell adhesion. Immunology. 1991 May;73(1):71–76. [PMC free article] [PubMed] [Google Scholar]
- Ju S. T., Ruddle N. H., Strack P., Dorf M. E., DeKruyff R. H. Expression of two distinct cytolytic mechanisms among murine CD4 subsets. J Immunol. 1990 Jan 1;144(1):23–31. [PubMed] [Google Scholar]
- Libby P., Ordovas J. M., Auger K. R., Robbins A. H., Birinyi L. K., Dinarello C. A. Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. Am J Pathol. 1986 Aug;124(2):179–185. [PMC free article] [PubMed] [Google Scholar]
- Mampaso F. M., Wilson C. B. Characterization of inflammatory cells in autoimmune tubulointerstitial nephritis in rats. Kidney Int. 1983 Mar;23(3):448–457. doi: 10.1038/ki.1983.41. [DOI] [PubMed] [Google Scholar]
- Matsumoto K., Atkins R. C. Glomerular cells and macrophages in the progression of experimental focal and segmental glomerulosclerosis. Am J Pathol. 1989 Apr;134(4):933–945. [PMC free article] [PubMed] [Google Scholar]
- Neilson E. G. Pathogenesis and therapy of interstitial nephritis. Kidney Int. 1989 May;35(5):1257–1270. doi: 10.1038/ki.1989.118. [DOI] [PubMed] [Google Scholar]
- Ohmori Y., Wyner L., Narumi S., Armstrong D., Stoler M., Hamilton T. A. Tumor necrosis factor-alpha induces cell type and tissue-specific expression of chemoattractant cytokines in vivo. Am J Pathol. 1993 Mar;142(3):861–870. [PMC free article] [PubMed] [Google Scholar]
- Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
- Rosenwasser L. J., Dinarello C. A. Ability of human leukocytic pyrogen to enhance phytohemagglutinin induced murine thymocyte proliferation. Cell Immunol. 1981 Sep 1;63(1):134–142. doi: 10.1016/0008-8749(81)90034-4. [DOI] [PubMed] [Google Scholar]
- Ryan G. B., Karnovsky M. J. An ultrastructural study of the mechanisms of proteinuria in aminonucleoside nephrosis. Kidney Int. 1975 Oct;8(4):219–232. doi: 10.1038/ki.1975.105. [DOI] [PubMed] [Google Scholar]
- Saito T., Atkins R. C. Contribution of mononuclear leucocytes to the progression of experimental focal glomerular sclerosis. Kidney Int. 1990 Apr;37(4):1076–1083. doi: 10.1038/ki.1990.88. [DOI] [PubMed] [Google Scholar]
- Schreiner G. F., Cotran R. S., Unanue E. R. Modulation of Ia and leukocyte common antigen expression in rat glomeruli during the course of glomerulonephritis and aminonucleoside nephrosis. Lab Invest. 1984 Nov;51(5):524–533. [PubMed] [Google Scholar]
- Silver B. J., Jaffer F. E., Abboud H. E. Platelet-derived growth factor synthesis in mesangial cells: induction by multiple peptide mitogens. Proc Natl Acad Sci U S A. 1989 Feb;86(3):1056–1060. doi: 10.1073/pnas.86.3.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]

