Adenosine and its metabolite,
inosine, have been described as molecules that participate in regulation of inflammatory response. The aim of this study was to investigate the effect of
adenosine and
inosine in a mouse model of
carrageenan-induced
pleurisy as well as the participation of
adenosine receptors in this response. Injection of
carrageenan into the pleural cavity induced an acute inflammatory response characterized by leukocyte migration, pleural exudation, and increased release of interleukin-1β and
tumor necrosis factor-α in pleural exudates. The treatment with
adenosine (0.3-100 mg/kg, i.p.) and
inosine (0.1-300 mg/kg, i.
p.) 30 min before
carrageenan injection reduced significantly all these parameters analyzed. Our results also demonstrated that A(2A) and A(2B) receptors seem to mediate the
adenosine and
inosine effects observed, since pretreatment with selective antagonists of
adenosine A(2A) (
ZM241385) and A(2B) (
alloxazine) receptors, reverted the inhibitory effects of
adenosine and
inosine in pleural
inflammation. The involvement of A(2) receptors was reinforced with
adenosine receptor agonist
CGS21680 treatment, since its anti-inflammatory effects were reversed completely and partially with
ZM241385 and
alloxazine injection, respectively. Moreover, the combined treatment with subeffective dose of
adenosine (0.3 mg/kg) and
inosine (1.0 mg/kg) induced a synergistic anti-inflammatory effect. Thus, based on these findings, we propose that
inosine contributes with
adenosine to exert anti-inflammatory effects in pleural
inflammation, reinforcing the notion that endogenous
nucleosides play an important role in controlling inflammatory diseases. This effect is likely mediated by the activation of
adenosine A(2) subtype receptors and inhibition of production or release of pro-inflammatory
cytokines.