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PMID: 1937825 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inhibition of endotoxin-induced interleukin-6 production by synthetic lipid A partial structures in human peripheral blood mononuclear cells.

Infection and immunity ·Vol. 59 ·No. 12 ·1991-12-00 ·Pages 4655-64

Wang MH, Flad HD, Feist W, Brade H, Kusumoto S, Rietschel ET, Ulmer AJ

Abstract

The effect of two synthetic lipid A partial structures, compound 406 (or LA-14-PP, identical in structure to the lipid A precursor, known as Ia or IVa) and compound 401 (lipid X), on the in vitro modulation of endotoxin (lipopolysaccharide)-induced interleukin-6 production by human blood mononuclear cells was investigated. Lipopolysaccharide of Salmonella abortus equi and synthetic Escherichia coli-type lipid A (compound 506, or LA-15-PP) had potent interleukin-6-inducing capacities. The maximum release of interleukin-6 was found after stimulation with 1 to 10 ng of lipopolysaccharide or 10 to 100 ng of synthetic E. coli-type lipid A per ml. Both synthetic lipid A partial structures (compounds 406 and 401) failed to induce interleukin-6 release. However, they inhibited lipopolysaccharide- or lipid A-induced interleukin-6 production in a dose-dependent manner. Inhibition was found not only in mononuclear cells but also in purified monocytes and was not due to a shift in the kinetics of cytokine production. Suppression was manifested in the early stage of interleukin-6 production. Inhibition was also found in the presence of recombinant gamma interferon, indicating that compound 406 and recombinant gamma interferon act in different, independent pathways. Our data, therefore, indicate that the inhibition of interleukin-6 production by lipid A partial structures may help elucidate the mechanism of interaction of the lipid A component of lipopolysaccharide with immune cells in the inflammatory reaction during gram-negative infection.

MeSH Terms
Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Glycolipids/pharmacology Humans Interferon-gamma/pharmacology Interleukin-6/biosynthesis Kinetics Leukocytes, Mononuclear/drug effects,metabolism Lipid A/analogs & derivatives,pharmacology Lipopolysaccharides/toxicity Recombinant Proteins
Chemicals
Glycolipids Interleukin-6 Lipid A Lipopolysaccharides Recombinant Proteins lipid A precursors, bacterial Interferon-gamma
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wang M H
Department of Immunology and Cell Biology, Borstel, Germany.
Flad H D
Feist W
Brade H
Kusumoto S
Rietschel E T
Ulmer A J
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.59.12.4655-4664.1991
Published
1991-12-00
Pages
4655-64
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC259092
Subset
IM
External Links
PubMed source DOI: 10.1128/iai.59.12.4655-4664.1991 PMC Full Text View journal details
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