Inhibition of septic shock in mice by an oligopeptide from the beta-chain of human chorionic gonadotrophin hormone.
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.
Khan
Nisar A
NA
Department of Immunology, Erasmus University and University Hospital Rotterdam, The Netherlands. khan@immu.fgg.eur.nl
Khan
Afshan
A
Savelkoul
Huub F J
HF
Benner
Robbert
R
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000652:urine; D000595:Amino Acid Sequence; D000818:Animals; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011247:Pregnancy / Q000276:immunology / Q000652:urine; D012772:Shock, Septic / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D018997:Chorionic Gonadotropin, beta Subunit, Human; D008070:Lipopolysaccharides; D009842:Oligopeptides; D010446:Peptide Fragments