The potential roles of cytokines, IL-5 and IL-8, and plasma cortisol in the anti-inflammatory actions of phosphodiesterase inhibitors in sensitized guinea-pig airways

Pulm Pharmacol Ther. 1997 Oct-Dec;10(5-6):277-85. doi: 10.1006/pupt.1998.0105.

Abstract

Ovalbumin (OvA) inhalation by sensitized guinea-pigs caused a pronounced rise in interleukin (IL)-5 in bronchoalveolar lavage (BAL) fluid at both 3 and 24 h after antigen exposure. The increased levels at 24 h were attenuated by the phosphodiesterase inhibitors Ro 20-1724 and aminophylline and by dexamethasone, all of which also attenuated the concurrent lung eosinophilia. The rise in IL-5 at 3 h was additionally attenuated by the PDE3 inhibitor, siguazodan, which failed to attenuate the eosinophilia at 24 h. These results suggest a pivotal action of these compounds on the later rise in IL-5. Ro 20-1724, aminophylline, siguazodan and dexamethasone attenuated a rise in IL-8 levels in BAL fluid at 3 h and the subsequent neutrophilia at 24 h. There was no increase in plasma ACTH at 3 and 24 h after OvA challenge but cortisol levels were elevated at 3 h. This was inhibited by Ro 20-1724, siguazodan and dexamethasone. Thus, elevation of plasma cortisol does not explain the anti-inflammatory actions of these compounds. Aminophylline, however, did raise plasma cortisol at both 3 and 24 h after antigen challenge which may be an important further mechanism of action for this compound.

Publication types

  • Comparative Study

MeSH terms

  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / pharmacology
  • Adrenocorticotropic Hormone / blood*
  • Aminophylline / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Bronchial Hyperreactivity / metabolism*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Dexamethasone / pharmacology
  • Eosinophils
  • Glucocorticoids / pharmacology
  • Guanidines / pharmacology
  • Guinea Pigs
  • Hydrocortisone / blood*
  • Interleukin-5 / metabolism*
  • Interleukin-8 / metabolism*
  • Lung / drug effects*
  • Lung / metabolism
  • Macrophages
  • Male
  • Neutrophils
  • Phosphodiesterase Inhibitors / pharmacology*
  • Pyridazines / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Guanidines
  • Interleukin-5
  • Interleukin-8
  • Phosphodiesterase Inhibitors
  • Pyridazines
  • Aminophylline
  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
  • siguazodan
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Hydrocortisone