Prostaglandin (PGE2), synthesized by cyclooxygenase-2 (COX-2), is associated with cellular immune tolerance during the process of cancer development. Induction of tolerance requires a specific environment in which dendritic cells and regulatory T cells (Tregs) play an essential role. It was recently shown that maturation of dendritic cells in the presence of indoleamine 2, 3-dioxygenase (IDO) results in activation of Tregs, and inhibition of COX-2 activity regulated IDO expression within the tumor microenvironment. Thus, we hypothesized that the tumor immune tolerance would be inhibited by COX-2 inhibitor and this inhibition would be mediated by IDO-dependent Tregs inhibition. The PGE2 in Lewis lung cancer cells (3LL) and serum of mice were measured for the evaluation of COX-2 inhibitors' local and systemic effects. The production of PGE2 in 3LL cells and serum of 3LL tumor-bearing mice were decreased by COX-2 inhibition. However, there were no significant differences in serum PGE2 levels among normal control and celecoxib-treated nontumor-bearing mice. The accumulation of Tregs was reduced in the celecoxib-treated 3LL tumor-bearing mice. In addition, the expressions of COX-2, IDO, and Foxp3 were reduced in the mice treated with a COX-2 inhibitor, and this was found to correlate with a reduction in the size of tumor mass and metastasis. These results suggest that the antitumor effects of COX-2 inhibitors seemed to be correlated with the inhibition of IDO and Tregs. Therefore, COX-2 inhibitors might provide a therapeutic strategy for Tregs-induced tumor immune tolerance.

The EGFR plays an essential role in goblet cell hyperplasia and mucus hypersecretion. EGFR has an intrinsic tyrosine kinase activity that, when activated, induces the production of MUC5AC through the signaling kinase cascade in the airway epithelium. We have investigated the effects of an EGFR tyrosine kinase inhibitor, gefitinib, on ovalbumin (OVA)-induced, allergic inflammation in airway epithelia of mice. OVA-sensitized mice were pretreated with gefitinib at two different doses (12.5 and 50 mg/kg) and then challenged with OVA. The OVA challenge increased the total cell count and eosinophil count in bronchoalveolar lavage fluid (BALF), as well as the concentrations of T-helper2 (Th2) cytokines, such as IL-4 and IL-13, overall eosinophil recruitment in the lung tissue and airway hyperresponsiveness (AHR). Pretreatment with gefitinib reduced the inflammatory cell counts and released cytokine concentrations (IL-4 and IL-13) in BALF, as well as eosinophil recruitment in the lungs and AHR, in a dose-dependent manner. This was associated with decreased EGFR and Akt phosphorylation. We showed that gefitnib inhibits EGFR and phosphoinositol 3'-kinase (PI3K)/Akt activation which were activated in OVA sensitized mice. These findings suggest that inhibitors of the EGFR cascade may have a role in the treatment of asthma.

Transfusion related acute lung injury (TRALI) is a serious, potentially life-threatening complication of transfusion therapy that is sometimes under diagnosed and under reported. Patients with TRALI present with dyspnea/respiratory distress and fever. The symptoms, signs and chest radiological findings in TRALI are similar to transfusion associated circulatory overload, which makes it is difficult to distinguish it from circulatory overload. Although the mortality rate in cases of TRALI is relatively low, TRALI is the third most common cause of fatal transfusion reactions next to ABO blood type incompatibility and hepatitis. Mild-to-moderate cases of TRALI may be misdiagnosed as volume overload. Recently, we encountered two cases where the patients suffered from dyspnea and fever after a transfusion. and review of the relevant literature. (Tuberc Respir Dis 2006; 61: 473-478)

Background: The smoking prevalence in asthma patients are similar to those in the general population. Asthma and active cigarette smoking can interact to create more severe symptoms, an accelerated decline in lung function and impaired therapeutic responses. Accordingly, asthmatics with a history of smoking were examined to define the clinical characteristics and lung function of smoking asthmatics. Methods: The medical records of 142 asthmatics with a known smoking history were reviewed. The patients were divided into three groups according to their smoking history -current smokers, former smokers and non-smokers. The clinical characteristics, lung function, and annual declines of the forced expiratory volume in one second (FEV1) were compared. Results: Fifty-three of the 142 patients (37%) were current smokers, 24 were former smokers (17%) and 65 were non-smokers (45%). The patients with a hospital admission history during the previous year included 16 current smokers (30%), 4 former smokers (17%) and 7 non-smokers (11%) (p=0.02). The mean FEV1 (% predicted) was 76.8±19.8%, 71.6±21.1% and 87.9±18.7% for current smokers, former smokers and non-smokers, respectively (p＜ 0.001). The FEV 1 /forced vital capacity (FVC) (ratio, %) values were 63.6±12.6%, 59.3±14.9% and 72.1±11.8% in current smokers, former smokers and non-smokers, respectively (p＜0.001). The corresponding mean values for the individual FEV1 slopes were not significant (p=0.33). Conclusion: Asthmatic smokers demonstrated higher hospital admission rates and lower lung function. These findings suggest that the smoking history is an important predictor of a poor clinical outcome in asthma patients.

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