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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. (J ALLERGY CLIN IMMUNOL 1996;98:400-7.)

Background: Ventilator-associated lung injury traditionally has been believed to result from the use of high pressures and multiple ventilation strategies have been tried to reduce injury and improve outcomes. Inflammatory cytokines are present in the lungs of newborns with BPD, oxidant injury may be another serious cause of lung injury and melatonin is known act as radical scavenger.Aims: The aim of current study was to evaluate lung inflammatory response in preterm infants with respiratory distress syndrome (RDS), mechanically ventilated with and without VG, as measured by proinflammatory cytokines (IL-6, IL-8, and TNFa) in tracheobronchial aspirate and by clinical outcome in a group of 55 newborns treated with melatonin. And 55 newborns without melatonin treatmentResults: Considering ventilator parameters and clinical outcome of the studied population, the two groups (treated and untreated) differed statistically significantly in maximal O2 concentration used, PIP (peak inspiratory pressure), PEEP (end expiratory pressure) as well as in the ventilatory modes used and in the oxygenation index (Median airway presure x O2 concentration / PaO2). Higher values were in untreated group. In both groups (treated and untreated) the values were higher in patients ventilated in the A/C mode and were lower in HFVO patients and in PSV with VG. Il-6 at time 0 presents values similar in treated and untreated nfants and equivalent in the six groups of ventilation modes; at 24 hr and at 71 hr IL-6 is higher all groups without a correlation with ventilation mode or treatment. At 7 days, IL-6 levels is significantly reduced in treated-newborns relative to those that received diluent and those ventilated in PSV and in GV had lower levels of IL-6. IL-8 values at 0 hr did not differ in the groups; at 24 hr there was a significant rise in the six groups; at 72 hr the melatonin treated newborns had a significant reduction in IL-8 serum levels that remain also at 7 days. TNFa levels did not differ? at 0 time. At 24 hr there were no differences from the from basal values in melatonin or untreated newborns. At 72 hr the melatonin-groups showed a statistical significant reduction compared to those in the diluent treated newborns which increased at 7 days, when higher TNFa levels were seen in untreated in relation to the group and to the ventilation mode. There were no differences in serum levels of any cytokines prior to the onset of treatment.Conclusion: Compared with the melatonin treated RDS newborns, the concentrations of inflammatory cytokines were significantly higher in the newborns given only the diluent. The current study suggests that reducing volutrauma will also reduced biotrauma as expressed by a reduction of inflammatory cytokines and an improved outcome; clearly, melatonin treatment provides benefits in this regard.