[HTML][HTML] Thalidomide protects mice against LPS-induced shock

AL Moreira, J Wang, EN Sarno… - Brazilian Journal of …, 1997 - SciELO Brasil
AL Moreira, J Wang, EN Sarno, G Kaplan
Brazilian Journal of Medical and Biological Research, 1997SciELO Brasil
Thalidomide has been shown to selectively inhibit TNF-a production in vitro by
lipopolysaccharide (LPS)-stimulated monocytes. TNF-a has been shown to play a pivotal
role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced
shock, we investigated the effects of thalidomide on the production of TNF-a and other
cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines
including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g were measured in the serum …
Thalidomide has been shown to selectively inhibit TNF-a production in vitro by lipopolysaccharide (LPS)-stimulated monocytes. TNF-a has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-a and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g 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-a levels were reduced by 93%, in a dose-dependent manner, and TNF-a mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-g. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death
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