Prevention of antigen-induced bronchial hyperreactivity and airway inflammation in sensitized guinea-pigs by tacrolimus.
We examined the effect of the immunosuppressive agent, tacrolimus (FK506), on antigen-induced bronchial hyperreactivity to acetylcholine and leukocyte infiltration into the airways of ovalbumin-challenged guinea-pigs. Subcutaneous injection of 0.5 mg/kg of FK506, 1 h before and 5 h after intra-nasal antigen challenge prevented bronchial hyperreactivity to aerosolized acetylcholine, eosinophilia in bronchoalveolar lavage (BAL) fluid and bronchial tissue and the invasion of the bronchial wall by CD4+ T-lymphocytes. FK506 also suppressed ovalbumin-induced increase in the number of leukocytes adhering to the pulmonary vascular endothelium and expressing alpha4-integrins. Inhibition by FK506 of antigen-induced bronchial hyperreactivity in sensitized guinea-pigs may thus relate to its ability to prevent the emergence of important inflammatory components of airway inflammation, such as eosinophil accumulation, as well as CD4+ T-lymphocyte infiltration into the bronchial tissue.
Lapa e Silva
J R
JR
Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil.
Ruffié
C
C
Lefort
J
J
Nahori
M A
MA
Vargaftig
B B
BB
Pretolani
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004804:Eosinophils / Q000502:physiology; D006168:Guinea Pigs; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D010047:Ovalbumin; D000109:Acetylcholine; D016559:Tacrolimus