Nucleosides like
adenosine,
uridine and their
nucleotide derivatives (e.g.
ATP and
UTP) play important roles in many cellular functions, sometimes by acting as signalling molecules through binding to specific P2
nucleotide receptors. P2 receptors are subdivided into P2X and P2Y subfamilies, the latter of which are
G-protein coupled receptors. P2Y receptors and
nucleoside transporters have been detected in human and rat lungs, where they mediate effects of interest in airway diseases. The aim of this study was to investigate whether
uridine has any anti-inflammatory properties in an
asthma-like animal model of
lung inflammation. The
Sephadex-induced
lung inflammation model in Sprague-Dawley rats was chosen mainly due to its localised inflammatory response and
uridine's limited oral bioavailability. The
dextran beads, with or without the addition of
uridine, were instilled intratracheally into the lungs, which were excised and examined after 24 h.
Sephadex alone led to massive oedema and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads.
Uridine reduced both the oedema and the infiltration of leukocytes significantly, measured as
lung wet weight and leukocyte counts in bronchoalveolar lavage fluid, respectively.
Uridine appeared to affect the tumour
necrosis factor (TNF) levels, although this could not be statistically confirmed due to large variations within the
Sephadex control group. We conclude that
uridine has anti-inflammatory effects, and that the exact mechanism(s) of action requires further study.