The Effects of β-Adrenoceptor Antagonists on Proinflammatory Cytokine Concentrations After Subarachnoid Hemorrhage in Rats

Abstract

Proinflammatory cytokines increase in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). Recent evidence suggested that beta-adrenoceptor antagonist could reduce proinflammatory cytokines. We conducted the present study to examine whether beta-adrenoceptor antagonists would reduce proinflammatory cytokine concentrations after SAH in rats. In Experiment 1, to investigate the time course of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), rats were randomized into groups: 1, 3, 6, and 12 h after SAH or sham operation. CSF and blood samples were obtained at each time point. In Experiment 2, to investigate the effects of beta-adrenoceptor antagonists on the IL-6 and TNF-alpha concentrations, rats were randomized into groups: 1) control group: SAH + normal saline, 2) propranolol group: SAH + propranolol, 3) metoprolol group: SAH + metoprolol, and 4) butoxamine group: SAH + butoxamine (beta(2)-adrenoceptor antagonist). CSF and blood samples were obtained 6 h after SAH. IL-6 and TNF-alpha concentrations in samples were measured. In Experiment 1, CSF IL-6 concentrations in the SAH groups increased markedly and peaked at 6 h after SAH, whereas CSF TNF-alpha concentrations in the SAH groups were consistently low. In Experiment 2, CSF IL-6 concentrations in the propranolol and butoxamine groups were significantly lower compared with those in the control group (P < 0.01 and P < 0.05 for each group). Plasma IL-6, CSF TNF-alpha, and plasma TNF-alpha concentrations were comparable in all four groups. CSF IL-6 concentrations increased in the acute stage of SAH and beta-adrenoceptor antagonists with a beta(2)-adrenoceptor blocking action suppressed this elevation of IL-6 concentrations after SAH in rats.