title: Thalidomide protects mice against LPS-induced shock.
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 endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-alpha and other cytokines and on animal survival. After injection of 100-350 micrograms LPS into mice, cytokines including TNF-alpha, IL-6, IL-10, IL-1 beta, 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%, in a dose-dependent manner, and TNF-alpha 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-1 beta, or IFN-gamma. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 micrograms to 300 micrograms in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021, USA. moreira@rockvax.rockefeller.edu
authors.forename: A L
authors.initials: AL
authors.lastname: Moreira
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: E N
authors.initials: EN
authors.lastname: Sarno
authors.forename: G
authors.initials: G
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology; D013792:Thalidomide / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D013792:Thalidomide