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, Masahiro Nishibori, N. Tanaka

Research output: Contribution to journalArticle

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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
Publication statusPublished - 2002

Fingerprint

Interleukin-18
Interleukin-2
Lipopolysaccharides
Blood Cells
Blood
Steroids
Cytokines
Intercellular Adhesion Molecule-1
Interferons
CD14 Antigens
Immunosorbents
Interleukin-12
Endotoxins
Interleukin-10
Assays
Healthy Volunteers
Anti-Inflammatory Agents
Up-Regulation
Chemical activation
Enzyme-Linked Immunosorbent Assay

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kodama, M., Takahashi, H. K., Iwagaki, H., Morichika, T., Yoshida, A., Yoshioka, H., ... Tanaka, N. (2002). Effect of steroids on lipopolysaccharide/interleukin 2-induced interleukin 18 production in peripheral blood mononuclear cells. Journal of International Medical Research, 30(2), 144-160.

Effect of steroids on lipopolysaccharide/interleukin 2-induced interleukin 18 production in peripheral blood mononuclear cells. / Kodama, M.; Takahashi, H. K.; Iwagaki, H.; Morichika, T.; Yoshida, A.; Yoshioka, H.; Morimoto, Y.; Nishibori, Masahiro; Tanaka, N.

In: Journal of International Medical Research, Vol. 30, No. 2, 2002, p. 144-160.

Research output: Contribution to journalArticle

Kodama, M, Takahashi, HK, Iwagaki, H, Morichika, T, Yoshida, A, Yoshioka, H, Morimoto, Y, Nishibori, M & Tanaka, N 2002, 'Effect of steroids on lipopolysaccharide/interleukin 2-induced interleukin 18 production in peripheral blood mononuclear cells', Journal of International Medical Research, vol. 30, no. 2, pp. 144-160.
Kodama, M. ; Takahashi, H. K. ; Iwagaki, H. ; Morichika, T. ; Yoshida, A. ; Yoshioka, H. ; Morimoto, Y. ; Nishibori, Masahiro ; Tanaka, N. / Effect of steroids on lipopolysaccharide/interleukin 2-induced interleukin 18 production in peripheral blood mononuclear cells. In: Journal of International Medical Research. 2002 ; Vol. 30, No. 2. pp. 144-160.
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