Effect of steroids on lipopolysaccharide/interleukin 2-induced interleukin 18 production in peripheral blood mononuclear cells.
Interleukin (IL) 18, a powerful inducer of the immunoregulatory cytokine interferon-gamma (IFN-gamma), 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-gamma 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.
Kodama
M
M
First Department of Surgery, Okayama University Medical School, Okayama, Japan.
Takahashi
H K
HK
Iwagaki
H
H
Itoh
H
H
Morichika
T
T
Yoshida
A
A
Yoshioka
H
H
Morimoto
Y
Y
Nishibori
M
M
Tanaka
N
N
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D020382:Interleukin-18; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D018664:Interleukin-12; D008776:Methylprednisolone Hemisuccinate; D007371:Interferon-gamma; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone