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Tumor necrosis factor and IL-1 in New Zealand Black/White mice. Enhanced gene expression and acceleration of renal injury

Brennan, Daniel C. and Yui, Mary A. and Wuthrich, Rudolf P. and Kelley, Vicki E. (1989) Tumor necrosis factor and IL-1 in New Zealand Black/White mice. Enhanced gene expression and acceleration of renal injury. Journal of Immunology, 143 (11). pp. 3470-3475. ISSN 0022-1767. http://resolver.caltech.edu/CaltechAUTHORS:20170303-151541749

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Abstract

TNF and IL-1 are potent immunologic and inflammatory cytokines. We have previously reported increased levels of mRNA for TNF alpha and IL-1 beta in MRL-lpr mice with lupus nephritis. To determine whether the increased levels of TNF and IL-1 mRNA are a more general feature of mice with lupus nephritis we studied cytokine gene expression in female NZB x NZW F1 (NZB/W) mice by Northern blot analysis. Enhanced steady state levels of mRNA for TNF alpha and IL-1 beta, but not IL-1 alpha, were detected in the renal cortices of animals with lupus nephritis. To determine whether administration of TNF or IL-1 would accelerate renal injury and mortality, we injected murine rTNF alpha or rIL-1 alpha i.p. into female NZB/W or C3H/FeJ mice at two doses, 2.0 micrograms or 0.2 micrograms, three times weekly for 2 or 4 mo beginning at 2 or 4 mo of age. Administration of the lower dose of each cytokine accelerated renal disease and mortality rate when treatment was initiated at 4 mo of age. At the higher dose, neither cytokine promoted disease. Treatment administered from 2-4 mo of age did not accelerate renal disease. This observation suggests that in order to cause renal injury, these cytokines must interact with other pathologic features present in these animals after 4 mo of age. These findings support the hypothesis that TNF and IL-1 can contribute to nephritis in murine models of lupus. Taken together with previously published data, we propose that TNF and IL-1 have differential dose effects on renal disease. The dose of TNF and IL-1 and the stage of disease activity dictate the pathogenic action of these cytokines.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.jimmunol.org/content/143/11/3470PublisherArticle
ORCID:
AuthorORCID
Yui, Mary A.0000-0002-3136-2181
Additional Information:© 1989 American Association of Immunologists. Received for publication July 24, 1989. Accepted for publication September 8, 1989. We would like to thank Dr. Anthony M. Jevnikar and Dr. Charles B. Carpenter for helpful comments on the manuscript. We would also like to thank Dr. Ivan Otterness for his generous gift of IL-1α. Supported by NIH Grants DK-36149 (V.E.K.), DK-40839 (V.E.K.), CA-48626 (V.E.K.), and AI-07918 (D.C.B.), and the Jules and Gwenn Knapp Charitable Foundation. R.P.W. is the recipient of a grant from the Swiss National Science Foundation.
Funders:
Funding AgencyGrant Number
NIHDK-36149
NIHDK-40839
NIHCA-48626
NIHAI-07918
Jules and Gwenn Knapp Charitable FoundationUNSPECIFIED
Swiss National Science Foundation (SNSF)UNSPECIFIED
Record Number:CaltechAUTHORS:20170303-151541749
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20170303-151541749
Official Citation:Tumor necrosis factor and IL-1 in New Zealand Black/White mice. Enhanced gene expression and acceleration of renal injury. D C Brennan, M A Yui, R P Wuthrich, V E Kelley The Journal of Immunology December 1, 1989, 143 (11) 3470-3475
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74727
Collection:CaltechAUTHORS
Deposited By: Donna Wrublewski
Deposited On:24 Mar 2017 16:37
Last Modified:24 Mar 2017 16:37

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