Effects of neurokinin depletion on airway inflammation induced by chronic antigen exposure.
We assessed the effects of neurokinin (tachykinin) depletion by capsaicin (CAP) treatment on airway inflammation induced by repeated ovalbumin (OA) aerosol exposures (twice a week for 4 wk) in guinea pigs. The animals were then anesthetized, tracheostomized, mechanically ventilated and challenged with ovalbumin aerosol. Maximal values of respiratory system resistance and elastance after antigen challenge were significantly lower in capsaicin-treated guinea pigs than in intact animals (p < 0.001). Morphometric analysis of noncartilaginous airways revealed less intense bronchoconstriction (p < 0.001) and peribronchiolar edema (p < 0.001) in capsaicin-treated guinea pigs. Chronic antigen exposure resulted in a significant increase in lymphocytes and eosinophils both in bronchoalveolar lavage (BAL) fluid and airway wall. Immunohistochemistry with monoclonal antibodies revealed that most of the lymphocytes present in airway wall were CD4+ T cells. Capsaicin treatment resulted in values of CD4+ T cells in airway wall significantly lower than non-capsaicin-treated guinea pigs (p < 0.005). This difference was not observed in eosinophil recruitment. Our results suggest that neurokinin release by sensory nerve terminals results in an amplification of the pulmonary inflammatory changes induced by chronic antigen exposure. In addition, neurokinins play a role in T-cell recruitment induced by chronic allergen exposure.
Tibério
I F
IF
Department of Medicine, Faculty of Medicine, University of São Paulo, Brazil.
Turco
G M
GM
Leick-Maldonado
E A
EA
Sakae
R S
RS
Paiva
S O
SO
do Patrocínio
M
M
Warth
T N
TN
Lapa e Silva
J R
JR
Saldiva
P H
PH
Martins
M A
MA
D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001980:Bronchi / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction; D018791:CD4 Lymphocyte Count; D002211:Capsaicin / Q000494:pharmacology; D004487:Edema / Q000473:pathology; D004548:Elasticity; D006168:Guinea Pigs; D007249:Inflammation; D008168:Lung / Q000473:pathology; D008170:Lung Compliance; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage; D015320:Tachykinins / Q000502:physiology*
D000336:Aerosols; D000941:Antigens; D015320:Tachykinins; D010047:Ovalbumin; D002211:Capsaicin