Local administration of uridine suppresses the cardinal features of asthmatic airway inflammation.
BACKGROUND
The immuno-modulatory properties of nucleotides such as adenosine or inosine, have been described extensively. Recently, the nucleoside uridine and its analogue 4-thiouridine have gained attention for their protective role in acute lung inflammation.


OBJECTIVE
In this study, we investigated the influence of uridine on asthmatic airway inflammation.


METHODS
We used the classical ovalbumin (OVA)-alum model, as well as a model of house dust mite-(HDM)-induced airway inflammation. The degree of inflammation was determined by bronchoalveolar lavage (BAL), histology, and measurement of bronchial hyperresponsiveness.


RESULTS
Intratracheal treatment of OVA-sensitized animals with uridine before allergen challenge resulted in a reduction in total BAL cells and BAL eosinophils. This was accompanied by reduced tissue infiltration and diminished production of T helper type 2-cytokines by mediastinal lymph node cells. Additionally, mice treated with uridine developed less bronchial hyperresponsiveness. Uridine was also effective in reducing airway inflammation in HDM-induced asthma. The protective effects of uridine were independent of myeloid dendritic cell (mDC) function, because in vitro pre-treatment of allergen-pulsed DCs with uridine did not alter the degree of inflammation. However, uridine inhibited the release of pro-inflammatory mediators in vivo and by cultured lung epithelial cells, suggesting an effect on lung structural cells.


CONCLUSIONS
In summary, we were able to show that uridine inhibits the classical features of asthmatic airway inflammation. As uridine supplementation is well tolerated in humans, it might be a new therapeutic approach for the treatment of bronchial asthma.
Müller
T
T
Department of Pneumology, University Medical Hospital Freiburg, Freiburg, Germany. tobias.mueller@uniklinikfreiburg.de
Grimm
M
M
de Vieira
R P
RP
Cicko
S
S
Dürk
T
T
Sorichter
S
S
Zissel
G
G
Idzko
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology; D014529:Uridine / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010047:Ovalbumin; D014529:Uridine