Effect of nedocromil sodium on allergen-induced airway responses and changes in the quantity of airway smooth muscle in rats.
BACKGROUND: Allergen exposures induce growth of airway smooth muscle in the Brown Norway rat. OBJECTIVE: The purpose of the study was to examine the role of mediators associated with the early and late responses in the induction of airway smooth muscle growth. METHODS: Nedocromil sodium was administered to block early and late responses in ovalbumin-sensitized and ovalbumin-challenged rats undergoing single or multiple challenges (5 times at 5-day intervals) with ovalbumin. Airway smooth muscle was quantitated by morphometry on lungs removed 2 days after the final challenge. RESULTS: Nedocromil sodium administered before ovalbumin challenge blocked both the early and late responses. When administered 2 hours after ovalbumin challenge, it also blocked the late response. Rats undergoing challenge with aerosolized ovalbumin five times at 5-day intervals were also treated with nedocromil before (n = 10) or 2 hours after (n = 10) each ovalbumin inhalation, respectively. The quantity of airway smooth muscle standardized for size was greater after ovalbumin challenge (0.069 +/- 0.005) compared with saline controls (0.033 +/- 0.003, p < 0.005). Nedocromil significantly reduced the airway smooth muscle (0.036 +/- 0.003, p < 0.005) when administered before ovalbumin. However, the airway smooth muscle in rats that received nedocromil 2 hours after ovalbumin challenge (0.046 +/- 0.003), although lower than in ovalbumin-challenged rats (p < 0.01), was still significantly higher than in saline-treated rats (p < 0.05). CONCLUSIONS: Allergen-induced early responses, late responses, and airway inflammation are antagonized by nedocromil. The mediators of both the early and late responses contribute to allergen-induced airway smooth muscle growth, a process that can be prevented by administration of nedocromil.