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.
Vigil
Silvana Virginia Gagliotti
SV
Department of Clinical Analysis, Center of Health Sciences, Federal University of Santa Catarina, Campus Universitário, Trindade, 88040-970, Florianópolis, SC, Brazil.
de Liz
Rafael
R
Medeiros
Yara Santos
YS
Fröde
Tânia Silvia
TS
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D016559:Tacrolimus / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007166:Immunosuppressive Agents; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D002351:Carrageenan; D009195:Peroxidase; D000243:Adenosine Deaminase; D016559:Tacrolimus; D007213:Indomethacin