Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors

Abraham Novogrodsky*, Alexey Vanichkin, Miriam Patya, Aviv Gazit, Nir Osherov, Alexander Levitzki

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Septic shock results from excessive stimulation of the host immune system, especially macrophages, by lipopolysaccharide (LPS), or endotoxin, which resides on the outer membrane of bacteria. Protein tyrosine kinase inhibitors of the tyrphostin AG 126 family protect mice against LPS-induced lethal toxicity. The protection correlates with the ability of these agents to block LPS-induced production of tumor necrosis factor α (TNF-α) and nitric oxide in macrophages as well as LPS-induced production of TNF-α in vivo. Furthermore, this inhibitory effect correlated with the potency of AG 126 to block LPS-induced tyrosine phosphorylation of a p42(MAPK) protein substrate in the murine macrophage.

Original languageEnglish
Pages (from-to)1319-1322
Number of pages4
Issue number5163
StatePublished - 27 May 1994


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