Efficacy of tacrolimus in inhibiting inflammation caused by carrageenan in a murine model of air pouch.

Background: Tacrolimus (Tac) is a macrolide immunosuppressant drug isolated from Streptomyces tsukubaensis, widely used in organ transplantation.

Objective: This study examined the effect of tacrolimus administered by oral route (p.o.) on inflammation in mouse subcutaneous air pouch triggered by carrageenan (Cg 1%).

Methods: The air pouch was induced as described by Benincá et al. [Benincá JP, Montanher AB, Zucolotto SM, Schenkel EP, FrödeTS. Anti-inflammatory effects of the Passiflora edulis: forma flavicarpa Degener inhibition of leukocytes, enzymes and pro-inflammatory cytokine levels in the air pouch model, in mice. Food Chem 2007; 104(3); 1097-1105.]. The inflammatory parameters (leukocytes, exudation, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, as well as nitrate/nitrate concentrations (NO(x)), interleukin-1 beta (IL-1beta), chemokine to neutrophil (KC) and tumor necrosis factor-alpha (TNF-alpha) levels were analysed 24 h after injection of carrageenan.

Results: Tacrolimus, indomethacin and dexamethasone significantly inhibited leukocytes, neutrophils and exudation (P<0.05) when they were administered 0.5 h before inflammation. These drugs, under the same conditions, decreased MPO and ADA activities (P<0.05), NO(x) and IL-1beta levels (P<0.01). Tacrolimus and indomethacin, but not dexamethasone, inhibited KC levels (P<0.01). On the other hand, tacrolimus and dexamethasone, but not indomethacin, decreased TNF-alpha levels (P<0.01).

Conclusions: Results of this study indicate that tacrolimus has an important anti-inflammatory property, showing not only inhibition of pro-inflammatory mediators release, but also inhibition of activated leukocyte infiltration into the site of inflammation. Furthermore, these results showed that most of the anti-inflammatory actions of tacrolimus were similar to those observed in animals treated with either indomethacin or dexamethasone.