Haptoglobin dampens endotoxin-induced inflammatory effects both in vitro and in vivo
Article first published online: 25 JAN 2005
Volume 114, Issue 2, pages 263–271, February 2005
How to Cite
Arredouani, M. S., Kasran, A., Vanoirbeek, J. A., Berger, F. G., Baumann, H. and Ceuppens, J. L. (2005), Haptoglobin dampens endotoxin-induced inflammatory effects both in vitro and in vivo. Immunology, 114: 263–271. doi: 10.1111/j.1365-2567.2004.02071.x
- Issue published online: 25 JAN 2005
- Article first published online: 25 JAN 2005
- Received 30 July 2004; revised 7 October 2004; accepted 8 October 2004.
- proinflammatory cytokines;
- septic shock
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-α, 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.