Haptoglobin dampens endotoxin-induced inflammatory effects both in vitro and in vivo.
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.
Arredouani
Mohamed S
MS
Laboratory for Experimental Immunology, Gasthuisberg University Hospital, Catholic University of Leuven, Leuven, Belgium. marredou@hsph.harvard.edu
Kasran
Ahmad
A
Vanoirbeek
Jeroen A
JA
Berger
Frank G
FG
Baumann
Heinz
H
Ceuppens
Jan L
JL
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
D016207:Cytokines; D006242:Haptoglobins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides