Greater involvement of neurokinins found in Guinea pig models of severe asthma compared with mild asthma.
BACKGROUND
Involvement of neurokinins in asthma has been previously pointed out by several reports. However, the relationship between neurokinins and the severity of asthma has remained unclear. We developed a model of mild asthma (model I) and severe asthma (model II) in guinea pigs, and investigated the function of neurokinins in both models.


METHODS
In models I and II, systemically sensitized guinea pigs were made to inhale ovalbumin once and three times, respectively. Substance P (SP) and neurokinin A (NKA) concentrations in the bronchoalveolar lavage fluid (BALF) were measured in models I and II. Then, the effects of a capsaicin pretreatment, which depletes neurokinins, in both animal models on airway narrowing induced by the last ovalbumin inhalation, airway hyperresponsiveness to inhaled methacholine, and eosinophil accumulation in BALF, were investigated.


RESULTS
SP concentration tended to increase and the NKA concentration increased significantly in model II, but not in model I. Capsaicin pretreatment significantly inhibited the late bronchial response that was observed 2-6 h after the last ovalbumin inhalation, airway hyperresponsiveness and eosinophil accumulation in model II. On the other hand, it had no effects on the responses in model I.


CONCLUSIONS
It is suggested that the more severe the disease, the greater the involvement of neurokinins.
Mukaiyama
Osamu
O
R&D Project Management Department, Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo, Japan. mukouy@sankyo.co.jp
Morimoto
Kiyoshi
K
Nosaka
Emi
E
Takahashi
Sakiko
S
Yamashita
Makoto
M
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000009:adverse effects; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016085:Bronchoconstrictor Agents / Q000009:adverse effects; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D008168:Lung / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride / Q000009:adverse effects; D015260:Neprilysin / Q000187:drug effects / Q000378:metabolism; D015288:Neurokinin A / Q000187:drug effects / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000209:etiology; D012720:Severity of Illness Index; D013373:Substance P / Q000187:drug effects / Q000378:metabolism*
D000485:Allergens; D015415:Biomarkers; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D013373:Substance P; D015288:Neurokinin A; D015260:Neprilysin; D002211:Capsaicin