Publications

Synthesis of interleukin-2 (IL-2) and expression of interleukin-2 receptors play central roles in T-cell activation, proliferation, and differentiation. The state of activation of T lymphocytes in the intestinal lamina propria was compared with that of circulating lymphocytes and lymphocytes isolated from the spleen or mesenteric lymph nodes of normal nonhuman primates. Lamina propria lymphocytes (LPL) had significantly higher proliferation in response to recombinant IL-2 compared with the other populations. In agreement with this finding, LPL had a significantly higher percentage of interleukin-2 receptor-positive (IL-2R+) cells as determined by staining with fluoresceinated monoclonal anti-IL-2R antibody. Two-color immunofluorescence staining showed that both CD4+ and CD8+ lamina propria T cells were IL-2R+. It was also found that the percentage of major histocompatibility complex class II-positive T cells was higher in the lamina propria. Northern blot analysis with a cDNA specific for the IL-2R showed that unstimulated LPL had easily detectable IL-2R mRNA, whereas no IL-2R mRNA was found in unstimulated lymphocyte populations from other sites. The activation of the IL-2R gene in LPL was not associated with the activation of other cellular genes (actin, major histocompatibility complex class I). Although no IL-2 bioactivity was measured in culture supernatants of unstimulated lymphocytes, concanavalin A-stimulated LPL produced significantly more IL-2 than other lymphocytes. This finding was confirmed at the molecular level as IL-2 mRNA was not detected in unstimulated LPL but was found in concanavalin A-stimulated LPL. Thus, normal lamina propria T lymphocytes have selective expression of genes associated with cell activation.

Traditionally, patients with acute airflow obstruction are treated with bronchodilator aerosols delivered by continuous flow nebulizers. While bronchodilator administration with the metered dose inhaler (MDI) and reservoir or spacer attachment is as effective as administration with the nebulizer in most settings, the former has not been widely accepted for treatment of acute airway obstruction in the emergency room. We compared the efficacy of the continuous flow nebulizer to that of the MDI with InspirEase (reservoir spacer) in 75 patients (45 men and 30 women), ages 18-73 (chi 44 years) who presented to the emergency room with acute asthma and COPD. Subjects in each group (22 COPD and 53 asthma) were randomly assigned to treatment with three puffs of metaproterenol (0.65 mg/puff) via the MDI with InspirEase plus nebulizer with placebo, or placebo MDI with InspirEase plus nebulizer with 15 mg metaproterenol in double blind fashion. Either treatment was given three times at 30 min intervals. The FEV1 and dyspnea scores according to the Borg scale were measured at baseline, 30 min after the first treatment, and 30 min after the third. There was no significant outcome difference between the two treatments in either diagnostic group. There also was no significant outcome difference for patients with baseline FEV1 less than 0.9L. Serum theophylline levels, the need for concomitant therapy with corticosteroids, or additional emergency room therapy after the study, hospitalizations and treatment side effects did not differ between treatment groups. We conclude that there is no demonstrable advantage of a continuous flow nebulizer over an MDI with InspirEase for the treatment of acute airflow obstruction.