Antiinflammatory effects of Tacrolimus in a mouse model of pleurisy

Abstract Introduction Tacrolimus is an antibiotic macrolide with immunosuppressant properties isolated from Streptomyces tsukubaensis . Objectives: This study evaluated whether the acute and systemic administration of Tacrolimus significantly interfered in leukocyte migration, exudation, myeloperoxidase and adenosine-deaminase and nitric oxide levels, as well as Interleukin-1 (IL-1β) and tumor necrosis factor alpha (TNFα) levels in a mouse model of pleurisy in comparison to those obtained with dexamethasone. Materials and methods Pleurisy was induced by carrageenan (Cg, 1%), bradykinin (BK, 10 nmol), histamine (HIS, 1 μmol) or substance P (PS, 20 nmol) administered by intrapleural route (ipl.) and the inflammatory parameters (cell migration and exudation) were analyzed 4 h after. In the model of pleurisy induced by carrageenan, other markers in the pleural fluid, such as cytokines (TNFα and Il-1β), nitrite/nitrate (NO x ), myeloperoxidase (MPO) and adenosine-deaminase (ADA) levels, were also studied. Dexamethaseone (0.5 mg/kg, i.p., 0.5 h before) was also analyzed in all protocols. Results In the pleurisy induced by carrageenan, Tacrolimus (1 mg/kg, i.p.) and dexamethasone (0.5 mg/kg, i.p.) administered 0.5 h before caused a significant decrease in leukocytes, neutrophils and exudation ( P  Tacrolimus and dexamethasone did not modify the blood's white or red cells ( P  > 0.05). Tacrolimus showed a long lasting antiinflammatory effect, inhibiting leukocytes and neutrophils for up to 24 h ( P  P  P  Tacrolimus inhibited ADA activity ( P  Tacrolimus, inhibited NO x levels ( P  Tacrolimus significantly inhibited cell migration induced by either bradykinin, histamine or substance P ( P  P  Tacrolimus only inhibited exudation caused by HIS ( P  Conclusions The results of the present work indicate that Tacrolimus showed important antiinflammatory properties against pleurisy in mice that are different from those caused by dexamethasone. The inhibition of proinflammatory cytokine (TNFα, IL-1β), enzyme (myeloperoxidase, adenosine-deaminase) and mediator (bradykinin, histamine, substance P) release and/or action appears to account for Tacrolimus 's actions.