Pyrrolidine dithiocarbamate augments IL-10, inhibits TNF-α, MIP-1α, IL-12, and nitric oxide production and protects from the lethal effect of endotoxin

Zoltán H. Németh, György Haskó, E. Sylvester Vizi

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

During endotoxemia, immune cells activated by lipopolysaccharide (LPS) produce various inflammatory mediators, including cytokines and nitric oxide (NO). The genes of several mediators are activated in part by the rapid binding of the transcription factor nuclear factor-kappa B (NF-κB) to its promoter. The induction of this transcription factor can be blocked by a wide range of antioxidants, including pyrrolidine dithiocarbamate (PDTC). Here we investigated in mice the effect of this compound on the plasma tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12), macrophage inflammatory protein-1α (MIP-1α), and nitric oxide (NO) response to intraperitoneal (i.p.) injection of LPS. Pretreatment of animals with PDTC (10-100 mg/kg) 30 min prior to LPS challenge (4 mg/kg, i.p.) decreased plasma TNF-α, IL-12, MIP-1α, and nitrite/nitrate (breakdown products of NO) concentrations, but enhanced plasma levels of IL-10. Moreover, pretreatment of mice with PDTC (10-100 mg/kg, i.p.) did not alter LPS-induced (4 mg/kg) production of IL-1α, IL-6, and IFN-γ. Finally, PDTC (100 mg/kg) protected the mice against LPS (100 mg/kg)-induced lethality. These results indicate that blockade of the NF-κB pathway by PDTC has potent anti-inflammatory action in systemic inflammatory processes.

Original languageEnglish
Pages (from-to)49-53
Number of pages5
JournalShock
Volume10
Issue number1
DOIs
Publication statusPublished - Jul 1998

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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