Adenosine increases interleukin 6 release and decreases tumour necrosis factor release from rat adrenal zona glomerulosa cells, ovarian cells, anterior pituitary cells, and peritoneal macrophages

Cytokine. 1997 Mar;9(3):187-98. doi: 10.1006/cyto.1996.0153.


Adenosine modifies interleukin 6 (IL-6) and tumour necrosis factor (TNF) release from immune tissues. Because adenosine alters endocrine function and endocrine cells secrete cytokines, its effects on IL-6 and TNF release from rat adrenals, ovaries, and anterior pituitaries were compared with its effects on cytokine release from rat peritoneal macrophages. Adenosine increased basal IL-6 release and decreased basal TNF release from adrenal zona glomerulosa and zona fasciculata/reticularis cells. IL-6 and TNF release from zona glomerulosa cells was greater (20x) than that of other adrenal cells. An A2 agonist modified adrenal IL-6 and TNF release at lower concentrations than an A1 agonist. Adenosine augmented adrenal IL-6 release stimulated by endotoxin (LPS), interleukin 1 beta (IL-1 beta), adrenocorticotrophic hormone, and angiotensin II. LPS- and IL-1 beta-stimulated adrenal TNF release was inhibited by adenosine. Adenosine increased IL-6 release and inhibited TNF release from ovarian cells. Anterior pituitary cells released IL-6, but no detectable TNF. Adenosine, via A2 receptors, stimulated IL-6 secretion from these cells. Peritoneal macrophage IL-6 release was increased and TNF release decreased by adenosine. Thus, in immune and endocrine tissues, adenosine increases IL-6 release, but inhibits TNF release.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology*
  • Adrenocorticotropic Hormone / pharmacology
  • Animals
  • Antineoplastic Agents / pharmacology
  • Cells, Cultured
  • Female
  • Interleukin-6 / metabolism*
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / metabolism*
  • Ovary / drug effects*
  • Ovary / metabolism
  • Phenethylamines / pharmacology
  • Pituitary Gland, Anterior / drug effects
  • Pituitary Gland, Anterior / metabolism*
  • Purinergic P1 Receptor Agonists
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism*
  • Xanthines / pharmacology
  • Zona Glomerulosa / drug effects
  • Zona Glomerulosa / metabolism*


  • Antineoplastic Agents
  • Interleukin-6
  • Phenethylamines
  • Purinergic P1 Receptor Agonists
  • Tumor Necrosis Factor-alpha
  • Xanthines
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • N(6)-cyclopentyladenosine
  • Adrenocorticotropic Hormone
  • 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine
  • Adenosine