Differential cytokine response in host defence mechanisms triggered by Gram-negative and Gram-positive bacteria, and the roles of gabexate mesilate, a synthetic protease inhibitor

H. Iwadou, Y. Morimoto, H. Iwagaki, S. Sinoura, Y. Chouda, M. Kodama, T. Yoshioka, S. Saito, T. Yagi, N. Tanaka

Research output: Contribution to journalArticle

18 Citations (Scopus)


Bacterial infection results in the production of inflammatory mediators and may be involved in the pathogenesis of sepsis and/or systemic inflammatory response syndrome. The effect of lipopolysaccharide (LPS), a major component of the outer surface of Gram-negative bacteria, and Staphylococcal enterotoxin B (SEB), a superantigen of Gram-positive bacteria, on cytokine production in peripheral blood mononuclear cells (PBMCs) was examined. LPS significantly increased the production of proinflammatory and anti-inflammatory cytokines, and SEB enhanced the production of helper T lymphocyte type cytokines. These results illustrated the different responses to Gram-negative and Gram-positive bacterial infections. The effect of gabexate mesilate, a synthetic protease inhibitor, on cytokine production and expression of the toll-like receptor (TLR) was also examined. The results suggest that gabexate mesilate-induced inhibition of tumour necrosis factor-α (TNF-α) and interleukin-18 (IL-18) production in LPS-stimulated PBMCs is due to the inhibition of the nuclear factor-κB activation pathway and/or inhibition of the processing pathway of pro-TNF-α and pro-IL-18, not to down-regulation of TLR-2 or TLR-4.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalJournal of International Medical Research
Issue number2
Publication statusPublished - Jan 1 2002



  • Cytokine
  • Lipopolysaccharide
  • Protease inhibitor
  • Staphylococcal enterotoxin B
  • Toll-like receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biochemistry, medical

Cite this