Recent reports demonstrate a role for
nucleotides as inflammatory modulators.
Uridine, for example, reduces oedema formation and leucocyte infiltration in a
Sephadex-induced
lung inflammation model. Tumour
necrosis factor (TNF) concentration was also reduced. Previous in vivo observations indicated that
4-thiouridine might have similar effects on leucocyte infiltration and TNF release. The aim of this study was thus to investigate the effects of
4-thiouridine in greater detail. We used a
Sephadex-induced acute
lung inflammation model in Sprague-Dawley rats. The
dextran beads were instilled intratracheally into the lungs, which were excised and examined after 24 h.
Sephadex alone led to massive oedema formation and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads. A significant increase in bronchoalveolar lavage fluid (BALF) content of TNF and
leukotrienes was also seen.
4-Thiouridine co-administration affected all variables investigated in this model, i.e. oedema, microscopic and macroscopic appearance of lung tissue, total leucocyte and differential leucocyte counts in BALF, TNF and
leukotrienes C(4) (LTC(4)), LTD(4 )and LTE(4) in BALF, indicating a reproducible anti-inflammatory effect. In conclusion, we have demonstrated that
4-thiouridine has anti-inflammatory effects similar to those of
uridine. To our knowledge, this is the first demonstration of pharmacological
4-thiouridine effects in vivo. The results suggest
nucleoside/
nucleotide involvement in inflammatory processes, warranting further studies on
nucleoside analogues as attractive new alternatives in the treatment of inflammatory diseases.