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PMID: 1987057 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Diphosphoryl lipid A obtained from the nontoxic lipopolysaccharide of Rhodopseudomonas sphaeroides is an endotoxin antagonist in mice.

Infection and immunity ·Vol. 59 ·No. 1 ·1991-01-00 ·Pages 441-4

Qureshi N, Takayama K, Kurtz R

Abstract

Diphosphoryl lipid A (DPLA) obtained from the nontoxic lipopolysaccharide (LPS) of Rhodopseudomonas sphaeroides ATCC 17023 did not induce interleukin-1 release by murine peritoneal macrophages. However, it blocked this induction by toxic deep-rough chemotype LPS (ReLPS) from Escherichia coli D31m4. Previously, we obtained similar results on the induction of tumor necrosis factor (TNF) by macrophages. These results showed that DPLA is able to block in vitro the induction of two important mediators of gram-negative bacterial sepsis. We then wanted to determine whether DPLA could also block the induction of TNF by LPS in animals. Mice were treated with 100 micrograms of R. sphaeroides DPLA and challenged 60 min later with 1.0 micrograms of ReLPS from E. coli. The serum TNF level was measured after 60 min. Treatment of mice with this DPLA blocked the rapid and transient rise of TNF caused by ReLPS. This result suggested that R. sphaeroides DPLA might be able to protect animals against endotoxin shock caused by gram-negative bacterial infection.

MeSH Terms
Animals Interleukin-1/biosynthesis Lipid A/analogs & derivatives,pharmacology Lipopolysaccharides/antagonists & inhibitors Mice Mice, Inbred C3H Rhodobacter sphaeroides/analysis Tumor Necrosis Factor-alpha/biosynthesis
Chemicals
Interleukin-1 Lipid A Lipopolysaccharides Tumor Necrosis Factor-alpha diphosphoryl lipid A
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Qureshi N
Mycobacteriology Research Laboratory, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.
Takayama K
Kurtz R
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24 references, click to expand
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
Published
1991-01-00
Pages
441-4
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC257761
Subset
IM
Grants
NIAID NIH HHS · AI-25856 · United States
NIGMS NIH HHS · GM-36054 · United States
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