Effect of steroids on lipopolysaccharide/interleukin 2-induced interleukin 18 production in peripheral blood mononuclear cells

M. Kodama, H. K. Takahashi, H. Iwagaki, T. Morichika, A. Yoshida, H. Yoshioka, Y. Morimoto, M. Nishibori, N. Tanaka

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Interleukin (IL) 18, a powerful inducer of the immunoregulatory cytokine interferon-γ (IFN-γ), presents upstream of the cytokine activation cascade in the inflammatory response. The anti-inflammatory properties of steroids permit their use in various conditions, although effects are transient and pathological states are not fully relieved by short-term steroidal use. We examined the effect of lipopolysaccharide (LPS)/IL-2 on the cytokine cascade in human peripheral blood mononuclear cells (PBMCs). We also examined the effect of steroids on LPS/IL-2-induced cytokine production in human PBMCs taken from healthy volunteers. Cell-free supernatant fractions were assayed for IL-18, IL-12, IL-2, IFN-γ and IL-10 protein, using enzyme-linked immunosorbent assays, and synergy between LPS and IL-2 in enhanced production of IL-18 was observed. Steroids suppressed the production of IL-18 and other secondary cytokines in LPS/IL-2-stimulated PBMCs, in a concentration- and time-dependent manner, although inhibition was incomplete even at high concentrations. Effects of steroid treatment on expression of membrane-bound LPS receptor antigen (mCD14) and intercellular adhesion molecule-1 (ICAM-1) in PBMCs were studied by flow cytometric analysis. Steroid treatment up-regulated mCD14 expression in a concentration-dependent manner, with no effect on ICAM-1 expression. These results suggest that the incomplete counteraction of steroids in the LPS/IL-2-initiating cytokine cascade is due, at least partly, to the up-regulation of mCD14 by steroid preparations, which increases susceptibility to bacterial endotoxins.

Original languageEnglish
Pages (from-to)144-160
Number of pages17
JournalJournal of International Medical Research
Volume30
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • CD14
  • Interleukin 18
  • Interleukin 2
  • Lipopolysaccharide
  • Steroids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biochemistry, medical

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