title: The effects of beta-adrenoceptor antagonists on proinflammatory cytokine concentrations after subarachnoid hemorrhage in rats.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Nara Medical University, Kashihara City, Nara, Japan. hkato@naramed-u.ac.j
authors.forename: Haruto
authors.initials: H
authors.lastname: Kato
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Satoki
authors.initials: S
authors.lastname: Inoue
authors.forename: Katsuji
authors.initials: K
authors.lastname: Hirai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Furuya
mesh_terms: D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D018836:Inflammation Mediators; D015850:Interleukin-6; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D002078:Butoxamine; D011433:Propranolol; D008790:Metoprolol