Immunoregulation of IL-6 secretion by endogenous and exogenous adenosine and by exogenous purinergic agonists in splenic tissue slices

Abstract

In recent years, the role of norepinephrine, opioids, and neuropeptide Y for sympathetic regulation of murine spleen cells has been characterised. In this study, we describe the role of exogenous and endogenous adenosine and exogenous P2X 1 and P2Y 1 agonists for spontaneous splenic IL-6 secretion from spleen slices. The P2X 1 agonist β,γ-methylene ATP inhibited IL-6 secretion at 10 −5 M, whereas the P2Y 1 agonist 2-methylthio ATP increased IL-6 secretion at 10 −6 to 10 −8 M. Furthermore, adenosine (at 5×10 −8, 10 −7, 5×10 −7 M) inhibited IL-6 secretion via A1 adenosine receptors, whereas an A2 A adenosine receptor agonist increased IL-6 secretion in the presence of 10 −7 M cortisol. To determine the effects of endogenous adenosine, electrical field stimulation was applied in order to release endogenous ATP, which yields adenosine after conversion from ATP. Electrical field stimulation markedly reduced IL-6 secretion, which was attenuated by the A1 antagonist DPCPX but not by the A2 antagonist 8-(3-Chlorostyryl)caffeine. Thus, via A1 adenosine receptors, adenosine was found to be a strong inhibitor of splenic IL-6 secretion. This study further expands our earlier description of the complexity of the local dialogue of sympathetic nerves and macrophages in lymphoid organs.