Cyclosporin A modulation of tumor necrosis factor gene expression and effects in vitro and in vivo

D. T. Nguyen, Mark Eskandari, L. E. DeForge, C. L. Raiford, R. M. Strieter, S. L. Kunkel, D. G. Remick*

*Corresponding author for this work

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

We investigated, in vitro and in vivo, the cyclosporin A (CsA) regulation of LPS-induced TNF gene expression and subsequent pathophysiologic changes. In vitro dose-response kinetics data showed that CsA inhibited TNF bioactivity in the supernatant without delaying its production, whereas Northern blot and in situ hybridization analysis demonstrated that CsA did not inhibit TNF mRNA expression. We then sought to examine the in vivo effects of CsA (75 mg/kg) in CBA/J mice that were primed with CFA, and injected 2 wk later with LPS. CsA demonstrated suppression of local levels (ascites) of TNF TNF ELISA. However, CsA did no decrease mRNA for TNF, or cell-associated TNF. In vivo kinetics studies were performed to show that CsA blocked both local (ascites) and systemic (plasma) LPS-induced TNF production without delaying these effects. CsA inhibited the neutrophilia and lymphopenia that developed after the LPS challenge, but did not block the lung neutrophilic infiltrate. These observations are helpful in understanding the role of the macrophage in CsA immunosuppression, particularly with regard to the ability of CsA to block LPS-induced TNF secretion.

Original languageEnglish (US)
Pages (from-to)3822-3828
Number of pages7
JournalJournal of Immunology
Volume144
Issue number10
StatePublished - 1990

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nguyen, D. T., Eskandari, M., DeForge, L. E., Raiford, C. L., Strieter, R. M., Kunkel, S. L., & Remick, D. G. (1990). Cyclosporin A modulation of tumor necrosis factor gene expression and effects in vitro and in vivo. Journal of Immunology, 144(10), 3822-3828.