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

Research output: Contribution to journalArticlepeer-review

Abstract

TNF and IL-1 are potent immunologic and inflammatory cytokines. We have previously reported increased levels of mRNA for TNFα and IL-1β 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 TNFα and IL-1β, but not IL-1α, 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 rTNFα or rIL-1α i.p. into female NZB/W or C3H/FeJ mice at two doses, 2.0 μg or 0.2 μg, 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.

Original languageEnglish (US)
Pages (from-to)3470-3475
Number of pages6
JournalJournal of Immunology
Volume143
Issue number11
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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