title: Haptoglobin dampens endotoxin-induced inflammatory effects both in vitro and in vivo.
abstract: We report that haptoglobin, an acute-phase protein produced by liver cells in response to interleukin-6 (IL-6), can modulate the inflammatory response induced by endotoxins. We provide evidence that haptoglobin has the ability to selectively antagonize lipopolysaccharide (LPS) effects in vitro by suppressing monocyte production of tumour necrosis factor-alpha, IL-10 and IL-12, while it fails to inhibit the production of IL-6, IL-8 and IL-1 receptor antagonist. In two animal models of LPS-induced bronchopulmonary hyperreactivity and endotoxic shock, haptoglobin knockout mice were more sensitive to LPS effects compared to their wild-type counterparts. The present data suggest that haptoglobin regulates monocyte activation following LPS stimulation. The increase in haptoglobin levels during an acute-phase reaction may generate a feedback effect which dampens the severity of cytokine release and protects against endotoxin-induced effects.
authors.affiliation: Laboratory for Experimental Immunology, Gasthuisberg University Hospital, Catholic University of Leuven, Leuven, Belgium. marredou@hsph.harvard.edu
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Arredouani
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kasran
authors.forename: Jeroen A
authors.initials: JA
authors.lastname: Vanoirbeek
authors.forename: Frank G
authors.initials: FG
authors.lastname: Berger
authors.forename: Heinz
authors.initials: H
authors.lastname: Baumann
authors.forename: Jan L
authors.initials: JL
authors.lastname: Ceuppens
mesh_terms: D000210:Acute-Phase Reaction; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003864:Depression, Chemical; D005434:Flow Cytometry; D006242:Haptoglobins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009000:Monocytes / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology
chemical_list: D016207:Cytokines; D006242:Haptoglobins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides