title: Stress-induced interleukin-6 release in mice is mast cell-dependent and more pronounced in Apolipoprotein E knockout mice.
abstract: OBJECTIVE
  Interleukin-6 (IL-6) is elevated in the serum of patients with coronary artery disease (CAD) and acute coronary syndromes (ACS). Intracoronary release of IL-6 was reported in ACS that can also be triggered by acute stress. In rats, acute restraint stress increases serum IL-6 and histamine, both of which may derive from mast cells. The current study was carried out in order to determine any possible difference in stress-induced IL-6 release in atherosclerotic mice and the contribution of mast cells, corticotropin-releasing hormone (CRH) and urocortin (Ucn).
  
  
  METHODS
  C57BL/6J, W/W(v) mast cell-deficient, Apolipoprotein E (ApoE) and CRH knockout (k/o) mice were stressed in plexiglass restraint chambers for 15 to 120 min. Serum corticosterone and IL-6 levels were measured. Some C57BL and ApoE k/o mice were pretreated with either the mast cell stabilizer disodium cromoglycate (cromolyn) or the peptide CRH receptor (CRH-R) antagonist Astressin. Cardiac mast cell activation was studied in both C57BL and ApoE k/o mice using light microscopy.
  
  
  RESULTS
  Acute stress increased serum IL-6 in mice, an effect much greater in ApoE k/o atherosclerotic mice. Stress-induced IL-6 release was absent in W/W(v) mast cell-deficient mice and it was partially inhibited by cromolyn in C57BL and ApoE mice. Mast cells were found adjacent to atherosclerotic vessels in ApoE k/o mice and were activated after stress. CRH k/o mice released more IL-6 in response to stress than their wild types, but Astressin significantly inhibited IL-6 release. Stress-induced IL-6 release may, therefore, be at least partly due to peripheral Ucn and/or CRH, with Ucn possibly overcompensation for CRH deficiency.
  
  
  CONCLUSIONS
  The present findings indicate that acute stress leads to mast cell-dependent serum IL-6 increase that may help explain stress-related coronary inflammation.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Man
authors.initials: M
authors.lastname: Huang
authors.forename: Xinzhu
authors.initials: X
authors.lastname: Pang
authors.forename: Katia
authors.initials: K
authors.lastname: Karalis
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D003327:Coronary Disease / Q000276:immunology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D013312:Stress, Physiological / Q000276:immunology*; D054832:Urocortins
chemical_list: D001057:Apolipoproteins E; D015850:Interleukin-6; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C104416:astressin; D003346:Corticotropin-Releasing Hormone; D004205:Cromolyn Sodium; D003345:Corticosterone