Invasive Tracheobronchial Aspergillosis with Bronchial Ulcers Complicated by Nontuberculous Mycobacterial Disease.

Invasive tracheobronchial aspergillosis (ITBA) complicated by nontuberculous mycobacteria (NTM) is rare. An 88-year-old man was admitted for hemoptysis. Bronchoscopy revealed bronchial ulcers, and a tissue biopsy showed Aspergillus fumigatus. He was diagnosed with ITBA, which improved with voriconazole. During treatment, infiltrative shadows appeared in his lungs, and bronchoscopy was performed once again. A non-necrotic epithelioid granuloma and Mycobacterium intracellulare were detected in the biopsy specimen. He was diagnosed with NTM disease. It is important to note that tracheobronchial ulcers may cause hemoptysis and to identify the etiology and treat it appropriately when multiple bacteria are found.

Haloperidol suppresses murine dendritic cell maturation and priming of the T helper 1-type immune response.

BACKGROUND: Haloperidol has immunomodulatory effects when used to treat patients with schizophrenia and also is used to sedate critically ill patients in the intensive care unit. Although the mechanism by which haloperidol affects immune function is unclear, one possibility is that it alters dendritic cell (DC) function. DCs are potent antigen-presenting cells that influence the activation and maturation of T lymphocytes. In this study, we investigated the in vitro and in vivo immunomodulatory effects of haloperidol on DC-mediated immune responses. METHODS: Using bone marrow-derived DCs in cell culture, we evaluated the effect of haloperidol on expression of costimulatory molecules (CD80 and CD86), major histocompatibility complex class ΙІ molecules, and the DC maturation marker CD83. DC culture supernatants also were evaluated for interleukin-12 p40 levels. In addition, we analyzed the effect of haloperidol on a mixed cell culture containing DCs and lymphocytes and measured the secretion of interferon-γ in the culture supernatants. We also assessed the in vivo effects of haloperidol on hapten-induced contact hypersensitivity responses. RESULTS: Haloperidol inhibited the expression of CD80, CD86, major histocompatibility complex class ΙІ, and CD83 molecules on DCs and the secretion of interleukin-12p40 in DC culture supernatants. In mixed cell cultures containing both T cells (CD4 and CD8α) and DCs, haloperidol-treated DCs suppressed the proliferation of allogeneic T cells and effectively inhibited the production of interferon-γ. In vivo, haloperidol reduced hapten-induced contact hypersensitivity responses. Furthermore, an antagonist to D2-like receptor suppressed the maturation of DCs in a manner similar to haloperidol. CONCLUSIONS: The results of our study suggest that haloperidol suppresses the functional maturation of DCs and plays an important role in the inhibition of DC-induced T helper 1 immune responses in the whole animal. Furthermore, the effect of haloperidol on DCs may be mediated by dopamine D2-like receptors. Together, these results demonstrate that administration of haloperidol suppresses DC-mediated immune responses.

Inhibitory roles of signal transducer and activator of transcription 3 in antitumor immunity during carcinogen-induced lung tumorigenesis.

Stat3 mediates a complex spectrum of cellular responses, including inflammation, cell proliferation, and apoptosis. Although evidence exists in support of a positive role for Stat3 in cancer, its role has remained somewhat controversial because of insufficient study of how its genetic deletion may affect carcinogenesis in various tissues. In this study, we show using epithelium-specific knockout mice (Stat3(Δ/Δ)) that Stat3 blunts rather than supports antitumor immunity in carcinogen-induced lung tumorigenesis. Although Stat3(Δ/Δ) mice did not show any lung defects in terms of proliferation, apoptosis, or angiogenesis, they exhibited reduced urethane-induced tumorigenesis and increased antitumor inflammation and natural killer (NK) cell immunity. Comparative microarray analysis revealed an increase in Stat3(Δ/Δ) tumors in proinflammatory chemokine production and a decrease in MHC class I antigen expression associated with NK cell recognition. Consistent with these findings, human non-small cell lung cancer (NSCLC) cells in which Stat3 was silenced displayed an enhancement of proinflammatory chemokine production, reduced expression of MHC class I antigen, and increased susceptibility to NK cell-mediated cytotoxicity. In addition, supernatants from Stat3-silenced NSCLC cells promoted monocyte migration. Collectively, our findings argue that Stat3 exerts an inhibitory effect on antitumor NK cell immunity in the setting of carcinogen-induced tumorigenesis.

4-Hydroxy-2-nonenal induces chronic obstructive pulmonary disease-like histopathologic changes in mice.

The α,ß-unsaturated aldehyde 4-hydroxy-2-nonenal (4-HNE) is an endogenous product of oxidative stress that is found at increased levels in the lungs of patients with chronic obstructive pulmonary disease (COPD) and animal models of this lung disorder. In the present study, levels of 4-HNE adducts were increased in two different mouse models of COPD. Challenging lungs with 4-HNE enlarged the airspace and induced goblet cell metaplasia of the airways in mice, two characteristics of COPD. 4-HNE induced the accumulation of inflammatory cells expressing high levels of MMP-2 and MMP-9. Our results indicate that 4-HNE production during oxidative stress is a key pathway in the pathogenesis of COPD.