Thalidomide protects mice against LPS-induced shock

• Autor(a) principal: Moreira,A.L.
• Data de Publicação: 1997
• Outros Autores: Wang,J., Sarno,E.N., Kaplan,G.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Brazilian Journal of Medical and Biological Research
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1997001000010
• topic: endotoxic shock; thalidomide; cytokines; inflammation

Thalidomide has been shown to selectively inhibit TNF-<!-- $MVD$:face("Symbol") --><FONT FACE="Symbol">a</font> production in vitro by lipopolysaccharide (LPS)-stimulated monocytes. TNF-<!-- $MVD$:face("Symbol") --><FONT FACE="Symbol">a</font> 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-<!-- $MVD$:face("Symbol") --><FONT FACE="Symbol">a</font> and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-<!-- $MVD$:face("Symbol") --><FONT FACE="Symbol">a</font>, IL-6, IL-10, IL-1ß, GM-CSF and IFN-<!-- $MVD$:face("Symbol") --><FONT FACE="Symbol">g</font> 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-<!-- $MVD$:face("Symbol") --><FONT FACE="Symbol">a</font> levels were reduced by 93%, in a dose-dependent manner, and TNF-<!-- $MVD$:face("Symbol") --><FONT FACE="Symbol">a</font> 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-<!-- $MVD$:face("Symbol") --><FONT FACE="Symbol">g</font>. 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