Airway eosinophilic inflammation is attenuated in conserved noncoding sequence-1-deficient mice.

BACKGROUND: Conserved noncoding sequence-1 (CNS-1) is an important regulatory element for T helper 2 cytokine expression. IL-4, IL-5 and IL-13 expression as well as serum IgE level were attenuated in CNS-1-/- mice. METHOD: CNS-1-/- and CNS-1+/+ mice were sensitized with ovalbumin (OVA) followed by antigen challenge. The number of eosinophils and T helper 2 cytokine concentration in the bronchoalveolar lavage fluid, OVA-specific IgE antibody (Ab) in the serum and bronchial responsiveness to methacholine were examined. RESULTS: Bronchoalveolar lavage fluid eosinophilia was significantly attenuated in CNS-1-/- mice compared to CNS-1+/+ mice, which were sensitized with OVA/aluminum once. OVA-specific IgE Ab was also attenuated. When mice were sensitized with OVA/aluminum twice, induction of eosinophilia and OVA-specific IgE Ab was not significantly different between CNS-1-/- and CNS-1+/+ mice. CONCLUSION: CNS-1 locus regulates eosinophilic inflammation in vivo.

IL-2-induced IL-9 production by allergen-specific human helper T-cell clones.

BACKGROUND: IL-9 is an important cytokine in allergic diseases such as asthma, atopic dermatitis, etc. T helper (Th) cells seem to be the main source of IL-9. Cellular and molecular mechanisms of IL-9 production by human Th cells have been poorly understood. METHODS: Dermatophagoides farinae(Der f)-specific Th clones were established from peripheral blood lymphocytes of atopic asthmatics, and cytokine synthesis in response to various stimuli was determined by specific ELISAs. RESULTS: IL-9 was produced by 14 of 27 human Th clones upon T cell receptor (TCR) stimulation, immobilized anti-CD3 antibody (Ab). IL-9 production was significantly enhanced by the addition of anti-CD28 Ab into the culture, indicating the role of costimulatory signal on IL-9 synthesis. Pharmacologically, IL-9 production was induced by ionomycin (IOM) alone, and enhanced by phorbol 12-myristate 13-acetate (PMA). rIL-2 induced IL-9 production by 8 out of 19 Th clones. IL-9 production by Th clones stimulated with immobilized anti-CD3 Ab was significantly suppressed by the addition of anti-IL-2 neutralizing Ab into the culture. CONCLUSION: Approximately half of the Der f-specific Th clones derived from atopic asthmatics produced IL-9 upon TCR stimulation. Ca(2+) signal, CD28 signal, and IL-2 receptor signal seem to play important roles in IL-9 production by human Th cells. Moreover, synthesis of IL-9, a Th2 cytokine, is dependent on IL-2, a Th1 cytokine, which is produced by Th cells themselves.

IL-9 production by peripheral blood mononuclear cells of atopic asthmatics.

BACKGROUND: IL-9 might play a critical role in pathogenesis and development of atopic asthma, but there are few reports on allergen-specific IL-9 production by peripheral blood mononuclear cells (PBMCs) obtained from adult asthmatics. METHODS: PBMCs were obtained from adult atopic asthmatics and incubated with Dermatophagoides farinae(Der f) extract for the designated time periods. The resulting supernatants were assayed for IL-9 by specific sandwich ELISA. RESULTS: IL-9 production was detectable on day 2 and reached maximum on day 6 after stimulation of PBMCs with Der f extract. IL-9 production in response to Der f extract increased in a dose-dependent manner. CD2- or CD4-bearing cell depletion completely abolished IL-9 production by PBMCs, while CD8-bearing cell depletion did not affect it. CONCLUSION: CD4+ lymphocytes are the principal source of IL-9 produced by PBMCs of adult atopic asthmatics.

[A case of non-small cell lung cancer accompanied with hemorrhage after chemotherapy including gemcitabine].

A 51-year-old man underwent left upper lobectomy due to pulmonary adenocarcinoma (cT2N1M0, stage IIB) in August, 2003. Since he turned out pT2N3M0 stage IIIB, he received combination chemotherapy with carboplatin and gemcitabine. During a second course chemotherapy, he was admitted again because of dyspnea and the deterioration of diffuse interstitial shadows in both lungs. He was treated with various antibiotics and corticosteroids. Unfortunately, he could not recover. An autopsy was performed. Microscopic features of the lung revealed diffuse alveolar damage and pulmonary hemorrhage. In this case, pulmonary hemorrhage should be considered as a complication of gemcitabine-induced lung injury.

[Clinical evaluation of meningeal carcinomatosis associated with primary lung cancer].

We evaluated diagnosis and treatment of four cases of meningeal carcinomatosis associated with primary lung cancer: case 1; small cell carcinoma (64 years old), case 2; small cell carcinoma (50 years old), case 3; adenocarcinoma (53 years old), and case 4; adenocarcinoma (55 years old). Determination of tumor markers in cerebrospinal fluid (CSF) together with the MRI findings that Gd-DTPA-enhanced T1-weighted image showing high intensity signal along the spinal cord was clinically useful in the diagnosis of meningeal carcinomatosis. Two of four patients received intrathecal chemotherapy and/or CSF drainage through Ommaya-Reservoir, resulting in dramatic improvement of various symptoms such as motor weakness and vesicorectal disorder. Intrathecal chemotherapy and placement of an Ommaya-Reservoir for CSF drainage should be considered to provide better Quality of Life (QOL) when patient can tolerate it.

Th2-cell-mediated chemokine synthesis is involved in allergic airway inflammation in mice.

Eosinophilic inflammation in the bronchial mucosa has been recognized as a prominent pathological feature of bronchial asthma. Th2 cells have been implicated in the local infiltration and activation of eosinophils. The migration of eosinophils as well as Th2 cells is controlled by chemokines, suggesting a crucial role of chemokines in the pathogenesis of bronchial asthma. To elucidate the mechanism by which Th2 cells induce eosinophilic inflammation, a Th2-cell-dependent murine model of asthma was employed in this study. Along with the infiltration of eosinophils and antigen-specific Th2 cells, CC chemokine receptor-3-active eotaxin, monocyte chemoattractant protein (MCP)-3 and RANTES, as well as CC chemokine receptor-3-inactive MCP-1 were produced in the lungs of Th2-cell-transferred mice after antigen provocation in vivo. On the other hand, differentiated antigen-specific Th2 cells produced MCP-3 and RANTES but not eotaxin or MCP-1 upon stimulation in vitro. Chemokines synthesized by Th2 cells and other cell types are involved in the development of eosinophilic inflammation in bronchial asthma.

IL-2-induced IL-13 production by allergen-specific human helper T cell clones.

BACKGROUND: Interleukin (IL)-5 and IL-13 are important cytokines in allergic diseases such as asthma and atopic dermatitis. We have reported that the production of IL-5 and IL-13 by mite-responsive T helper cells (Th) is controlled under similar signal requirements, but precise mechanisms are not yet well characterized. METHODS: Allergen-specific Th clones were established from peripheral blood lymphocytes of atopic asthmatics, and cytokine synthesis in response to various stimuli was determined by specific ELISAs. IL-13 gene expression was enumerated by quantitative real-time PCR. RESULTS: IL-13 production was clearly induced by IL-2. IL-13 mRNA expression was also induced. CONCLUSION: The IL-2 signal by itself causes IL-13 synthesis independent of T cell receptor stimulation.

Inhalation of tobramycin in a patient with aspiration pneumonia as a result of medullary stroke.

A 78-year-old man suffered from refractory aspiration pneumonia as a result of a minor medullary stroke. The only neurological symptom observed in this patient was difficulty in swallowing. He was managed with i.v. hyperalimentation with termination of oral intake, including water. However, he still experienced several episodes of aspiration pneumonia. As he was considered to have a bacterial infection because of silent aspiration of colonized oropharyngeal material, inhalation of tobramycin was introduced and successful control of airway infection was attained.