Protective effects of Tacrolimus, a calcineurin inhibitor, in experimental periodontitis in rats.
OBJECTIVE
Periodontitis is a well-appreciated example of leukocyte-mediated bone loss and inflammation with pathogenic features similar to those observed in other inflammatory diseases, such as arthritis. Since Tacrolimus, is an immunomodulatory drug used for the treatment of some cases of arthritis, we hypothesized that it may modulate periodontal disease.


METHODS
Using a murine model of ligature-induced periodontal disease, we assessed the effects of daily administrations of Tacrolimus (1mg/kg body weight) on bone loss, enzymatic (myeloperoxidase) analysis, differential white blood cells counts, airpouch exudate and cytokine expression for 5-30 days.


RESULTS
Radiographic, enzymatic (myeloperoxidase) and histological analysis revealed that Tacrolimus reduced the severity of periodontitis. More specifically, Tacrolimus suppressed the expression of serum interleukin (IL-1beta), tumour necrosis factor (TNF-alpha), IL-6, airpouch exudate PGE(2) and leukocytosis usually observed after the induction of periodontitis. Tacrolimus treatment in periodontitis-induced rats conferred protection against the inflammation-induced tissue and bone loss associated with periodontitis, through a mechanism involving IL-1beta, TNF-alpha and IL-6.


CONCLUSIONS
The effects of Tacrolimus on periodontal disease pathogenesis may provide clues to a novel approach to host modulation therapy in destructive periodontal disease.
Guimarães
M R
MR
Department of Physiology and Pathology, Dental School of Araraquara (UNESP), State University of São Paulo, Araraquara, São Paulo, Brazil.
Nassar
P O
PO
Andia
D C
DC
Nassar
C A
CA
Spolidorio
D M P
DM
Rossa
C
C
Spolidorio
L C
LC
D016301:Alveolar Bone Loss / Q000517:prevention & control; D000818:Animals; D065095:Calcineurin Inhibitors; D015232:Dinoprostone / Q000032:analysis; D004195:Disease Models, Animal; D005881:Gingiva / Q000187:drug effects / Q000201:enzymology; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000097:blood / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D007964:Leukocytosis / Q000517:prevention & control; D008297:Male; D010518:Periodontitis / Q000201:enzymology / Q000517:prevention & control*; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects
D065095:Calcineurin Inhibitors; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D015232:Dinoprostone; D016559:Tacrolimus