Pharmacologic inhibitors of tumor necrosis factor production exert differential effects in lethal endotoxemia and in infection with live microorganisms in mice

J Infect Dis. 1995 Feb;171(2):393-9. doi: 10.1093/infdis/171.2.393.


Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are principal mediators of septic shock; inhibition of TNF-alpha production may ameliorate outcome in severe infections. Pentoxifylline, chlorpromazine, and thalidomide inhibit TNF-alpha production. Their effects were tested in lethal endotoxemia in sensitized mice. Only chlorpromazine significantly improved survival. Chlorpromazine and pentoxifylline significantly reduced postendotoxin circulating TNF-alpha, by 89% and 76%, respectively. Chlorpromazine also significantly reduced IL-1 beta and soluble TNF receptor-P75. No drug improved survival in Klebsiella pneumoniae-infected mice despite significantly lower circulating TNF-alpha concentrations in chlorpromazine- or pentoxifylline-treated animals. The three compounds decreased circulating TNF-alpha in Candida albicans-infected mice, but survival was not influenced. In neutropenic mice, chlorpromazine had no influence on candida in organs, but in normal mice, Candida counts in kidneys were higher in chlorpromazine-treated mice. Thus, inhibition of TNF-alpha production was of no benefit in K. pneumoniae infection and worsened outcome in C. albicans infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candidiasis / drug therapy
  • Chlorpromazine / therapeutic use*
  • Female
  • Interleukin-1 / blood
  • Kidney / microbiology
  • Klebsiella Infections / drug therapy
  • Klebsiella pneumoniae / pathogenicity
  • Mice
  • Neutropenia / metabolism
  • Pentoxifylline / therapeutic use*
  • Receptors, Tumor Necrosis Factor / analysis
  • Shock, Septic / drug therapy*
  • Shock, Septic / mortality
  • Thalidomide / therapeutic use*
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Interleukin-1
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Thalidomide
  • Pentoxifylline
  • Chlorpromazine