Effect of the nitric oxide inhibitor, L-N-G-monomethylarginine, on accumulation of interleukin-6 and interleukin-8, and nuclear factor-kappa B activity in a human endothelial cell line

H F Galley, S J Nelson, J Dhillon, A M Dubbels, N R Webster

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objective: To determine the effect of the nitric oxide synthase inhibitor, L-N-G-monomethylarginine, on interleukin-6 and interleukin-8 accumulation, and nuclear factor-kappa B expression in an endothelial cell model of sepsis.

Design: Controlled cell culture experiments examining the immunomodulatory effects of nitric oxide synthase inhibition.

Subjects: A human endothelial cell line (EA.hy926).

Measurements and Results: Cells were incubated with tumor necrosis factor-alpha and interleukin (IL)-1 beta in the presence of L-N-G-monomethylarginine (L-NMMA). IL-6 and IL-8 were measured in culture supernatants using enzyme immunoassay. Nuclear factor-kappa B was measured using electrophoretic mobility shift assay and was quantified using phosphorimaging. IL-6 accumulation was decreased (p < .05) and IL-8 accumulation increased (p < .01) with L-NMMA. Increased nuclear factor-kappa B expression in stimulated cells was unaltered on exposure to L-NMMA. Cell viability was unaffected.

Conclusions: Excessive production of nitric oxide has been implicated in septic shock, and the use of nitric oxide synthase inhibitors has been suggested. The immunoregulatory actions of nitric oxide synthase inhibitors affects the profile of cytokine release. This effect is not mediated through modulation of nuclear factor-kappa B. These findings have implications for the use of nitric oxide synthase inhibiting agents in septic shock.

Original languageEnglish
Pages (from-to)908-912
Number of pages5
JournalCritical Care Medicine
Volume27
Publication statusPublished - 1999

Keywords

  • cytokine
  • interleukin-6
  • interleukin-8
  • nitric oxide
  • endothelium
  • L-N-G-monomethylarginine
  • septicemia
  • transcription factors
  • nuclear factor-kappa B
  • TUMOR-NECROSIS-FACTOR
  • HUMAN SEPTIC SHOCK
  • SEPSIS SYNDROME
  • TRANSCRIPTION FACTOR
  • SYNTHASE ACTIVITY
  • IL-8 EXPRESSION
  • GENE-EXPRESSION
  • CYTOKINE LEVELS
  • SERUM LEVELS
  • ACTIVATION

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