PMID- 7844376
OWN - NLM
STAT- MEDLINE
DCOM- 19950309
LR  - 20190512
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 171
IP  - 2
DP  - 1995 Feb
TI  - Pharmacologic inhibitors of tumor necrosis factor production exert differential 
      effects in lethal endotoxemia and in infection with live microorganisms in mice.
PG  - 393-9
AB  - 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.
FAU - Netea, M G
AU  - Netea MG
AD  - Department of Internal Medicine, University Hospital Nijmegen, Netherlands.
FAU - Blok, W L
AU  - Blok WL
FAU - Kullberg, B J
AU  - Kullberg BJ
FAU - Bemelmans, M
AU  - Bemelmans M
FAU - Vogels, M T
AU  - Vogels MT
FAU - Buurman, W A
AU  - Buurman WA
FAU - van der Meer, J W
AU  - van der Meer JW
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Interleukin-1)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - SD6QCT3TSU (Pentoxifylline)
RN  - U42B7VYA4P (Chlorpromazine)
SB  - IM
MH  - Animals
MH  - Candidiasis/drug therapy
MH  - Chlorpromazine/*therapeutic use
MH  - Female
MH  - Interleukin-1/blood
MH  - Kidney/microbiology
MH  - Klebsiella Infections/drug therapy
MH  - Klebsiella pneumoniae/pathogenicity
MH  - Mice
MH  - Neutropenia/metabolism
MH  - Pentoxifylline/*therapeutic use
MH  - Receptors, Tumor Necrosis Factor/analysis
MH  - Shock, Septic/*drug therapy/mortality
MH  - Thalidomide/*therapeutic use
MH  - Tumor Necrosis Factor-alpha/analysis/*antagonists & inhibitors
EDAT- 1995/02/01 00:00
MHDA- 1995/02/01 00:01
CRDT- 1995/02/01 00:00
PHST- 1995/02/01 00:00 [pubmed]
PHST- 1995/02/01 00:01 [medline]
PHST- 1995/02/01 00:00 [entrez]
AID - 10.1093/infdis/171.2.393 [doi]
PST - ppublish
SO  - J Infect Dis. 1995 Feb;171(2):393-9. doi: 10.1093/infdis/171.2.393.