Premium
Central injection of nitric oxide synthase inhibitors increases peripheral interleukin‐6 and serum amyloid A: involvement of adrenaline from adrenal medulla
Author(s) -
Song DongKeun,
Im YeongBin,
Jung JunSub,
Yan JiJing,
Huh SungOh,
Suh HongWon,
Kim YungHi
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703273
Subject(s) - endocrinology , medicine , prazosin , yohimbine , antagonist , nitric oxide synthase , chemistry , nitric oxide , adrenal medulla , intraperitoneal injection , catecholamine , receptor , biology
Accumulating evidence suggests that plasma levels of interleukin‐6 (IL‐6), a major cytokine stimulating the synthesis of acute phase proteins, are intimately regulated by the central nervous system (CNS). In the present study, effects of intracerebroventricular (i.c.v) injection of N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME) or 7‐nitroindazole, nitric oxide synthase (NOS) inhibitors, on plasma IL‐6 levels and peripheral IL‐6 mRNA expression were examined in mice.L ‐NAME (0.1–2 μg per mouse i.c.v.) and 7‐nitroindazole (0.2–2 μg per mouse i.c.v.) induced a dose‐dependent increase in plasma IL‐6 levels and a subsequent increase in circulating serum amyloid A, a liver acute‐phase protein. In contrast, an intraperitoneal (i.p.) injection of L ‐NAME up to the dose of 25 μg per mouse had no effect. Pretreatment with yohimbine (α 2 ‐adrenergic antagonist; 1 mg kg −1 i.p.), or ICI‐118,551 (β 2 ‐adrenergic antagonist; 2 mg kg −1 i.p.), but not with prazosin (α 1 ‐adrenergic antagonist; 1 mg kg −1 i.p.), nor betaxolol (β 1 ‐adrenergic antagonist; 2 mg kg −1 i.p.), significantly inhibited the central L ‐NAME‐induced plasma IL‐6 levels. I.c.v. (50 μg per mouse) or i.p. (100 mg kg −1 ) pretreatment with 6‐hydroxydopamine had no effect on central L ‐NAME‐induced plasma IL‐6 levels. However, intrathecal (i.t.) pretreatment with 6‐hydroxydopamine (20 μg per mouse) markedly inhibited central L ‐NAME‐induced plasma IL‐6 levels. Both yohimbine (1.5 μg per mouse i.t.) and ICI‐118,551 (1.5 μg per mouse i.t.) were effective in inhibition of central L ‐NAME‐induced plasma IL‐6 levels. There was an elevation of base‐line plasma IL‐6 levels in adrenalectomized animals. The adrenalectomy‐enhanced levels were not further increased by central L ‐NAME.L ‐NAME (2 μg per mouse i.c.v.) induced an increase in IL‐6 mRNA expression in liver, spleen, and lymph node. These results suggest that NOS activity in the brain tonically down‐regulates peripheral IL‐6 by inhibiting adrenaline release from the adrenal medulla.British Journal of Pharmacology (2000) 130 , 41–48; doi: 10.1038/sj.bjp.0703273