Urinary leukotriene E4 (LTE4) concentrations have been measured in six asthmatic patients with aspirin sensitivity and in five asthmatic subjects tolerant of aspirin, before and after provocation with aspirin or placebo. Aspirin-sensitive subjects showed an average 21% fall in FEV1 after aspirin challenge whereas control individuals had a 2% fall in FEV1 after ingestion of 100 mg aspirin. The resting urinary LTE4 concentrations in asthmatic subjects sensitive to aspirin were 243 pg/mg creatinine (range 50 to 1,041), and these were on average sixfold greater than those in control asthmatic subjects. Further, there was a mean fourfold increase in urinary LTE4 levels at 3 to 6 h after aspirin, but not placebo, challenge in aspirin-sensitive asthmatic subjects that was not seen in the control asthmatic individuals. Leukotriene release may play a central role in the mechanisms of asthmatic attacks produced by aspirin ingestion.

The response of the brown trout to a single, short (c. 2 min) incidence of handling stress was monitored for a period of 1 month post-stress. Significant changes were found in feeding behaviour, in the levels of plasma cortisol, glucose and lactate, in the concentration of circulating lymphocytes and in the degree of epidermal mucification. No changes were detected in the growth rate and coefficient of condition, in the levels of plasma thyroxine, in the concentrations of circulating erythrocytes, neutrophils and thrombocytes or in the thickness of the epidermis. The time-course for recovery of each parameter was examined and from this it was concluded that a minimum of 2 weeks was required for complete recovery and a return to normality.

The cyclo-oxygenase (COX) pathway converts arachidonic acid to prostaglandins, prostaBackground -There are two isoforms of cyclin, and thromboxane A 2 . 1 2 There are two cyclo-oxygenase (COX), namely COX-1 isoforms of COX, namely COX-1 and COX-2.3 and COX-2. COX-1 is constitutively ex-COX-1 (PGH synthase-1) was initially purified pressed in most tissues and in blood plateand cloned from sheep vesicular glands and is lets. The metabolites derived from COXconstitutively expressed in most tissues and in 1 are probably involved in cellular houseblood platelets. The metabolites derived from keeping functions. COX-2 is expressed COX-1 are probably involved in cellular houseonly following cellular activation by inkeeping functions such as coordinating the acflammatory stimuli and is thought to be tions of circulating hormones and regulating involved in inflammation. vascular homeostasis. COX-2 (PGH synthaseMethods -The expression of COX-1 and 2) shares approximately 62% amino acid hom-COX-2 isoenzymes has been studied in the ology with COX-1 3 and is expressed only folbronchial mucosa of 10 normal and 18 lowing cellular activation by inflammatory asthmatic subjects, 11 of whom had stimuli such as growth factors, cytokines and aspirin-sensitive asthma (ASA) and mitogens in fibroblasts and by bacterial liposeven had non-aspirin-sensitive asthma polysaccharide in monocytes and macro-(NASA).phages. [4][5][6][7] The observations that the expression Results -There was a significant fourfold of COX-2 is induced by inflammatory meand 14-fold increase, respectively, in the diators in immune cells and that its expression epithelial and submucosal cellular exis inhibited by glucocorticoids suggest that inpression of COX-2, but not of COX-1, in ducible COX-2 may produce prostanoids inasthmatic patients. There was no sigvolved in inflammation. Since enhanced nificant difference in the total number of cytokine expression is a feature of asthmatic cells staining for either COX-1 or COX-2 airways, we reasoned that COX-2 might be between subjects with ASA and NASA, but augmented in this disease. the number and percentage of mast cellsPatients with bronchial asthma form a that expressed COX-2 was significantly inheterogeneous group and asthmatic individuals

This study was performed to determine whether lipoxin A4 (LXA4) inhalation in asthmatic subjects has an effect on airways response. Eight subjects (six asthmatic, two normal) attended for bronchial inhalation challenge with LXA4. In three of these subjects (two asthmatics, one normal) blood pressure, pulse, and symptoms before and after challenge were recorded. Subsequently five male patients with mild asthma (22 to 34 yr of age) reattended for bronchial inhalation challenge with either leukotriene C4 (LTC4) or the combination of LTC4 and 1 x 10(-4) M LXA4. After inhalation of each dose of agonist SGaw and V25 were measured. Airway responsiveness was determined by the concentration of agonist in the nebulizer required to induce a 35% fall in SGaw (PC35). There was no effect of LXA4 inhalation on SGaw, V25, blood pressure, pulse, or symptoms. There was a significant shift of the SGaw and V25 dose-response curve to the right after inhalation challenge with LTC4 combined with 1 x 10(-4) M LXA4 as compared with that after inhalation challenge with LTC4 alone (p less than 0.01 and p less than 0.025, respectively). Thus, LXA4 may modulate LTC4-induced airway obstruction and may act as an endogenous sulfidopeptide leukotriene receptor antagonist.

Immunized mice after inhalation of specific antigen have the following characteristic features of human asthma: airway eosinophilia, mucus and Th2 cytokine release, and hyperresponsiveness to methacholine. A model of late-phase allergic pulmonary inflammation in ovalbumin-sensitized mice was used to address the role of the alpha4 integrin (CD49d) in mediating the airway inflammation and hyperresponsiveness. Local, intrapulmonary blockade of CD49d by intranasal administration of CD49d mAb inhibited all signs of lung inflammation, IL-4 and IL-5 release, and hyperresponsiveness to methacholine. In contrast, CD49d blockade on circulating leukocytes by intraperitoneal CD49d mAb treatment only prevented the airway eosinophilia. In this asthma model, a CD49d-positive intrapulmonary leukocyte distinct from the eosinophil is the key effector cell of allergen-induced pulmonary inflammation and hyperresponsiveness.