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.
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.
Department of Pharmacology, Welsh School of Pharmacy, University of Wales Cardiff, Wales, UK.
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H
Danahay
K J
KJ
Broadley
P J
PJ
McCabe
A T
AT
Nials
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S
Sanjar
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils; D005938:Glucocorticoids / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000097:blood*; D015848:Interleukin-5 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages; D008297:Male; D009504:Neutrophils; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D006146:Guanidines; D015848:Interleukin-5; D016209:Interleukin-8; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D000628:Aminophylline; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; C056215:siguazodan; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone