Jeroen Vanoirbeek

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‐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.

Sputum cytokine mapping reveals an 'IL-5, IL-17A, IL-25-high' pattern associated with poorly controlled asthma

Asthma is a heterogeneous disease with various clinical, inflammatory and molecular phenotypes. We studied sputum cytokine mRNA expression patterns in an unselected group of adult asthma patients to characterize the underlying inflammatory process.

Sensitization to Inhaled Ryegrass Pollen by Collateral Priming in a Murine Model of Allergic Respiratory Disease

Background: Mouse models of asthma suffer from the necessity to prime the animals by injections before respiratory exposure. Our aim was to develop a mouse model that mimics the progression of human allergic disease upon low-dose inhaled allergen exposure. Methods: Mice were primed intraperitoneally to ovalbumin (OVA) before they were exposed repeatedly to aerosols of either OVA, ryegrass (Lolium perenne) pollen extract, or both concomitantly. The sensitization to ryegrass pollen proteins was evaluated by measurement of specific serum antibody, by the respiratory response to a challenge with ryegrass pollen extract and by lung cytokine production after challenge. Results: Inhalation of ryegrass pollen extract alone did not result in sensitization. Sensitization to inhaled ryegrass pollen proteins, however, did occur in mice that had been sensitized to OVA by intraperitoneal injections and were then exposed to inhaled ryegrass pollen extract and OVA simultaneously. T and B cell priming was ascertained by ryegrass pollen-specific IgG1 and IgE antibody production and by induction of airway inflammation and of Th2 cytokine mRNA transcripts in the lungs upon airway challenge with ryegrass pollen extract. A progressive spread of the IgE/IgG1 response to different ryegrass pollen proteins could be visualized in immunoblots by comparing antibody patterns at day 56 and 86. Conclusions: Low-dose inhalatory allergen exposure results in sensitization when airways are exposed at the same time to another allergen to which the animals are already sensitized. This model can help to unravel the mechanisms that underlie the development and progression of respiratory allergic diseases.