Distinct effects of endogenous interleukin-23 on eosinophilic airway inflammation in response to different antigens.

BACKGROUND: The role of interleukin (IL)-23 in asthma pathophysiology is still controversial. We examined its role in allergic airway inflammation in response to two distinct antigens using IL-23-deficient mice. METHODS: Allergic airway inflammation was evaluated in wild-type and IL-23p19(-/-) mice. Mice were sensitized to ovalbumin (OVA) or house dust mite (HDM) by intraperitoneal injection of antigen and their airways were then exposed to the same antigen. Levels of antigen-specific immunoglobulins in serum as well as cytokines in bronchoalveolar or peritoneal lavage fluid and lung tissue were determined by enzyme-linked immunosorbent assay and/or quantitative polymerase chain reaction. RESULTS: Deficiency of IL-23p19 decreased eosinophils and Th2 cytokines in bronchoalveolar lavage fluid (BALF) of OVA-treated mice, while it increased BALF eosinophils of HDM-treated mice. Peritoneal injection of OVA with alum, but not of HDM, induced local synthesis of IL-6, IL-10, and IL-23. Systemic production of antigen-specific IgG1 was partially dependent on IL-23. In contrast, airway exposure to HDM, but not to OVA, induced IL-23p19 mRNA expression in the lungs. In IL-23p19-deficient mice, HDM-exposed lungs did not exhibit the induction of IL-17A, which negatively regulates eosinophilic inflammation. CONCLUSIONS: Different antigens induced IL-23 at different part of the body in our similar asthma models. Endogenous IL-23 production at the site of antigen sensitization facilitates type-2 immune responses, whereas IL-23 production and subsequent IL-17A synthesis in the airways suppresses allergic inflammation.

[Concurrent chemoradiotherapy with carboplatin and docetaxel for stage III non-small-cell lung cancer].

The efficacy and toxicity of concurrent chemoradiotherapy with carboplatin (AUC=5) +docetaxel (70 mg/m(2)) were analyzed retrospectively in 20 patients with stage III non-small-cell lung cancer (NSCLC). The median age of the patients was 65 years (range, 53-73 years). The performance status (ECOG), clinical stage, and tumor histology of the patients were as follows: PS: PS 0, 12 patients; PS 1, 8 patients; disease stage: stage III A, 6 patients; stage III B, 14 patients; tumor histology: adenocarcinoma, 11 patients; squamous cell carcinoma, 6 patients; large cell carcinoma, 3 patients. The median number of treatment courses administered was 4. The median survival time was 23 months, and the 2-year survival rate was 50%. The median progression free survival was 17.5 months. The response rate was 75%. Common toxicities included grade 3/4 neutropenia (95%), grade 3 esophagitis (5%), grade 3 anorexia (30%), grade 3 febrile neutropenia (35%) and grade 5 radiation pneumonitis (5%). Further studies are warranted to evaluate the efficacy and toxicity of this regimen.

[A case of advanced adenocarcinoma of the lung which maintained complete response for 5 years by treatment with gefitinib].

A 73-year-old woman smoker presented with dyspnea on exertion due to massive left pleural effusion. A CT scan after drainage of the pleural effusion demonstrated a nodule in the left lung, and cytology of the pleural effusion showed adenocarcinoma. We diagnosed advanced adenocarcinoma of the lung, and clinical stage IIIB. Chemotherapy with carboplatin and docetaxel was discontinued after the second course because of anorexia, and gefitinib was administered from October 2004. The lung nodule and pleural effusion had disappeared on CT by November 2004. A complete response continued for 5 years. We report a 5-year complete response in a case of advanced adenocarcinoma of the lung by treatment with gefitinib.

[A case of miliary tuberculosis showing acute respiratory distress syndrome in rheumatoid arthritis].

A 62-year-old man, treated with corticosteroids and immunosuppressants for rheumatoid arthritis, visited hospital with high fever and dyspnea on exertion. A CT scan of the chest demonstrated bilateral diffuse ground glass opacities. On the basis of the findings of the CT scan, he was initially given a diagnosis of interstitial pneumonia. He was then referred to our hospital and admitted to the intensive care unit (ICU), where because of progressive respiratory failure, he was put on mechanical ventilation. A bronchoscopy specimen after intubation turned out to be positive for acid-fast bacilli, which were confirmed to be mycobacterium tuberculosis by a polymerase chain reaction test. He was given a diagnosis of miliary tuberculosis complicated with acute respiratory distress syndrome (ARDS). He died of respiratory failure despite treatment with antituberculosis drugs. The autopsy revealed necrotizing epithelioid granulomas in both lungs, mediastinal lymph nodes, the liver, both kidneys, vertebrae and other organs. Diffuse alveolar damage was also found in both lungs. It is often difficult to detect disseminated nodules in the miliary tuberculosis with ARDS. Miliary tuberculosis should be suspected in patients in an immunosuppressant state with rheumatoid arthritis, and who have respiratory symptoms or fever of unknown origin.

[A case of early-onset COPD with recurrent pneumothorax].

Early-onset chronic obstructive pulmonary disease (COPD) is designated as onset under age 50. We report a case of early-onset COPD with recurrent pneumothorax. A 29-year-old woman visited our hospital with productive cough and dyspnea on exertion. CT scan of the chest demonstrated severe panlobular emphysema. A pulmonary function test showed a reduction in FEV1.0 (41% of the predicted value). A diagnosis of severe COPD was made. Her symptoms and pulmonary function improved after the treatment of inhaled corticosteroid, long-acting beta2-agonist, and anti-cholinergic drugs. She had pneumothorax at least 8 times in the right lung. The level of alpha1-antitrypsin was normal. On the basis of the characteristics of the appearance of the chest X-ray and CT scan, the possibility of bronchiolitis obliterans, lymphoangioleiomyomatosis or Langerhans cell histiocytosis was thought to be low. We considered that several factors, such as high susceptibility, pulmonary infection during her childhood, bronchial asthma, malnutrition, smoking history from an early age, and long-term passive exposure to cigarette smoke may have contributed to the development of early-onset COPD in the present case.

[Combination chemotherapy with carboplatin and docetaxel for elderly patients with non-small-cell lung cancer].

The efficacy and toxicity of treatment with carboplatin (AUC= 5)+ docetaxel (70mg/m2) were analyzed retrospectively in 27 elderly patients with advanced non-small-cell lung cancer (NSCLC) aged 70 years or more. The median age of the patients was 74 years (range, 70-83 years). The performance status (ECOG), clinical stage, and tumor histology in the patients were as follows: PS: PS 0, 12 patients; PS 1, 11 patients; PS 2, 4 patients; disease stage: stage IIIA, 5 patients; stage IIIB, 11 patients; stage IV, 11 patients; tumor histology: adenocarcinoma, 18 patients; squamous cell carcinoma, 9 patients. The median number of treatment cycles administered was 4. The median survival time was 11.1 months and the 1-year survival rate was 40.7%. The response rate was 33.3%. The major toxicities were leukopenia and neutropenia; grade 3/4 neutropenia occurred in 22 patients (81.5%). Nonhematologic toxicities were generally mild, including grade 3 anorexia in 13 patients (48.1%) and grade 3 febrile neutropenia in 9 patients (33.3%). No treatment-related deaths were observed. Thus, it was concluded that the combination of carboplatin + docetaxel is a feasible, well-tolerated, and effective regimen for fit elderly patients with NSCLC. Prospective studies comparing carboplatin + docetaxel with third-generation single-agent chemotherapy or non-platinum-based combination chemotherapy are needed to confirm the efficacy and safety of this drug combination.