Involvement of steroids in anti-inflammatory effects of PK11195 in a murine model of pleurisy

• Published in: Mediators of Inflammation Vol. 2004; no. 2; pp. 93 - 103
• Main Authors: da Silva, Marcelo Barreto Spillere, Farges, Roseli Coimbra, Fröde, Tânia Silvia
• Format: Journal Article
• Language: English
• Published: United States Hindawi Limiteds 01.04.2004; Hindawi Limited
• Subjects: Adenosine Deaminase - metabolism; Aminoglutethimide - metabolism; Aminoglutethimide - pharmacology; Animals; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Carrageenan - administration & dosage; Disease Models, Animal; Female; GABA-A Receptor Agonists; Isoquinolines - metabolism; Isoquinolines - pharmacology; Isoquinolines - therapeutic use; Leukocytes - drug effects; Leukocytes - metabolism; Male; Mice; Nitrates - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitrites - metabolism; PK11195; Pleurisy; Pleurisy - chemically induced; Pleurisy - drug therapy; Pleurisy - immunology; Receptors, GABA-A - immunology; Steroid Synthesis; Steroids - therapeutic use; PK11195; Nitric oxide; Pleurisy; Steroid Synthesis
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1080/09629350410001688486

BACKGROUND: Studies on peripheral benzodiazepine receptor function have yielded a diverse list of activities of which the anti-inflammatory effects need to be further examined. Aims: To evaluate the role of steroids, nitric oxide and adenosine-deaminase in the anti-inflammatory effect of PK11195. Methods: Pleurisy was induced by intrapleural injection of carrageenan in mice pre-treated or not with PK11195. Leukocytes, exudation, adenosine-deaminase (ADA) activity and nitric oxide (NO) level were measured. Steroid involvement was evaluated by pretreatment with D,L-aminogluthetimide before PK11195. Results: Leukocytes, exudation and NO levels were reduced by PK11195 in the early (4 h) phase. In the late (48 h) phase, PK11195 decreased leukocytes and ADA activity. D,L-aminogluthetimide reversed the effect of PK11195 on exudate (4 h), as well as total and differential leukocytes and NO levels (48 h). Conclusions: Steroids, NO and ADA are implicated in the anti-inflammatory action of PK11195.