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


OBJECTIVE
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 pre-treatment 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.
da Silva
Marcelo Barreto Spillere
MB
Department of Clinical Analysis, Center of Health Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis, SC, Brazil.
Farges
Roseli Coimbra
RC
Fröde
Tânia Silvia
TS
D000243:Adenosine Deaminase / Q000378:metabolism; D000616:Aminoglutethimide / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D002351:Carrageenan / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D011963:Receptors, GABA-A / Q000276:immunology; D013256:Steroids / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines; D009566:Nitrates; D009573:Nitrites; D011963:Receptors, GABA-A; D013256:Steroids; D000616:Aminoglutethimide; D009569:Nitric Oxide; D002351:Carrageenan; D000243:Adenosine Deaminase; C037850:PK 11195