Thalidomide protects mice against LPS-induced shock
Rev. bras. pesqui. méd. biol
; Braz. j. med. biol. res;30(10): 1199-207, Oct. 1997. ilus, graf
Article
in En
| LILACS
| ID: lil-201538
Responsible library:
BR1.1
ABSTRACT
Thalidomide has been shown to selectively inhibit TNF-alpha production in vitro by lipopolysaccharide (LPS)-stimulated monocytes. TNF-alpha has been shown to play a pivotal role in the pathophysiology of endototoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the introduction of TNF-alpha and other cytokines and on animal survival. After injecton of 100-350 mug LPS into mice, cytokines including TNF-alpha, IL-6, IL-10, IL-1beta, GM-CSF and IFN-gamma were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-alpha levels were reduced by 93 percent, in a dose-dependent manner, and TNF-alpha mRNA expression in the spleens of mice was reduced by 70 percent. Serum IL-6 levels were also inhibited by 50 percent. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1beta or IFN-gamma. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 mug to 300 mug in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death.
Full text:
1
Collection:
01-internacional
Database:
LILACS
Main subject:
Shock, Septic
/
Thalidomide
/
Lipopolysaccharides
/
Disease Models, Animal
Limits:
Animals
Language:
En
Journal:
Braz. j. med. biol. res
/
Rev. bras. pesqui. méd. biol
Journal subject:
BIOLOGIA
/
MEDICINA
Year:
1997
Document type:
Article
/
Project document
Country of publication:
Brazil