Effect of thalidomide on chemokine production by human microglia

James R. Lokensgard, Shuxian Hu, Esther M. Van Fenema, Wen S. Sheng, Phillip K. Peterson

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Thalidomide, a psychoactive drug that readily crosses the blood-brain barrier, has been shown to possess immunomodulatory attributes, including the inhibition of cytokine production by monocytes and microglia. In this study, we investigated the effect of thalidomide on chemokine production by human microglial cells. Microglial cells were stimulated with lipopolysaccharide, a key cell-wall component of gram-negative bacteria responsible for meningitis, and production of chemokines (regulated upon activation normally T cell expressed and secreted [RANTES], monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1β, and interleukin [IL]-8) was examined by ELISA. Thalidomide treatment was found to cause potent and selective inhibition of IL-8 production in a dose-responsive manner. This inhibition was associated with decreased intracellular IL-8 staining as well as reduced transcription of IL-8 mRNA. In addition, thalidomide treatment of lipopolysaccharide-stimulated microglia inhibited the activation of protein NF-κB, a transcription factor known to be important for IL-8 production. These results suggest thalidomide could have a therapeutic role in acute bacterial meningitis through inhibition of IL-8-mediated neutrophil chemotaxis.

Original languageEnglish (US)
Pages (from-to)983-987
Number of pages5
JournalJournal of Infectious Diseases
Volume182
Issue number3
DOIs
StatePublished - 2000

Bibliographical note

Funding Information:
Financial support: US Public Health Service grants MH-57617, DA-04381, and DA-09924.

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