Document Detail


Inhibition of septic shock in mice by an oligopeptide from the beta-chain of human chorionic gonadotrophin hormone.
MedLine Citation:
PMID:  11924526     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human chorionic gonadotrophin (hCG) is a heterodimeric placental glycoprotein hormone required in pregnancy. In human pregnancy urine and in commercial hCG preparations (c-hCG) it occurs in a variety of forms, including breakdown products. Several reports have suggested modulation of the immune system by intact hormone, but such effects of breakdown products have not been reported. In a related article (Hum Immunol 62:1315, 2001), it is reported that a 400-2000 Dalton (Da) fraction from c-hCG and from human pregnancy urine inhibits Th1-mediated diabetes in NOD mice. The active component(s) were called natural (immuno)modulatory pregnancy factor(s) (NMPF). This study reports that a single treatment with the same low molecular weight NMPF fraction up to 24-h after high dose lipopolysaccharide (LPS) injection inhibited septic shock in mice. This counteracting effect of NMPF paralleled the downregulation of the effects of LPS on the production of macrophage migration inhibitory factor (MIF) by spleen cells, on the plasma level of liver aminotransferase, and on the expression of several splenic lymphocyte and macrophage surface markers. Based on the primary structure of the beta-chain of hCG a synthetic hexapeptide Valine-Leucin-Proline-Alanine-Leucine-Proline (VLPALP) was designed, which demonstrated it to have the same protective effects as the 400-2000 Da NMPF fraction. These results indicate a new strategy for the treatment of septic shock and the potential of therapeutic use of this synthetic oligopeptide.
Authors:
Nisar A Khan; Afshan Khan; Huub F J Savelkoul; Robbert Benner
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Human immunology     Volume:  63     ISSN:  0198-8859     ISO Abbreviation:  Hum. Immunol.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-03-27     Completed Date:  2002-10-10     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8010936     Medline TA:  Hum Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-7     Citation Subset:  IM    
Affiliation:
Department of Immunology, Erasmus University and University Hospital Rotterdam, The Netherlands. khan@immu.fgg.eur.nl
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MeSH Terms
Descriptor/Qualifier:
Adjuvants, Immunologic / pharmacology,  urine
Amino Acid Sequence
Animals
Chorionic Gonadotropin, beta Subunit, Human / chemistry,  pharmacology*
Female
Humans
Killer Cells, Natural / drug effects,  immunology
Lipopolysaccharides / toxicity
Mice
Mice, Inbred BALB C
Molecular Weight
Oligopeptides / chemistry,  pharmacology*
Peptide Fragments / chemistry,  pharmacology
Pregnancy / immunology,  urine
Shock, Septic / drug therapy,  etiology,  prevention & control*
T-Lymphocyte Subsets / drug effects,  immunology
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Chorionic Gonadotropin, beta Subunit, Human; 0/Lipopolysaccharides; 0/Oligopeptides; 0/Peptide Fragments

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