What are the risk factors for postoperative home oxygen therapy in patients with lung cancer?

Background: Home oxygen therapy (HOT) is used to treat chronic respiratory diseases and is sometimes required in patients with lung cancer after radical surgery. We aimed to identify the risk factors for postoperative home-based oxygen therapy in patients with lung cancer. Methods: Patients who underwent surgery for primary lung cancer at Chiba University Hospital between January 2019 and March 2021 were included. Patients who did not undergo complete resection, died in hospital after surgery, or used oxygen therapy preoperatively were excluded. Eligible patients were divided into HOT and non-HOT groups. They were retrospectively analyzed for risk factors for postoperative HOT using medical records in a multivariate analysis. Results: A total of 410 patients were included in this study, 24 (5.9%) of whom required HOT after surgery. The HOT group comprised significantly more men, heavy smokers, and patients with pulmonary comorbidities, low percent forced expiratory volume, percent forced vital capacity, predicted postoperative forced expiratory volume in 1 s, and postoperative pulmonary complications on univariate analysis. In a multivariate analysis, independent risk factors for postoperative HOT were pulmonary comorbidities [odds ratio (OR): 5.94; 95% confidence interval (CI): 1.64-21.5; P=0.002) and postoperative pulmonary complications (OR: 5.39; 95% CI: 2.14-13.5; P<0.001). The postoperative HOT application rate was calculated according to a formula developed for this purpose. Conclusions: Comorbid pulmonary diseases and postoperative pulmonary complications were significantly associated with postoperative HOT in patients with lung cancer.

Can modified frailty index predict postoperative complication after lung cancer surgery?

PURPOSE: The impact of the modified frailty index (mFI) on postoperative complications after lung cancer surgery was investigated. METHODS: Patients who underwent lung cancer surgery in 2017 were included. 30-day postoperative mortality and morbidity were evaluated according to their Clavien-Dindo classification. mFI values are presented as the sum of values of 11 included items. Logistic regression was used to assess the effect of mFI on postoperative severe complication incidence. RESULTS: Among 190 patients considered, severe postoperative complications (Grade 3 or more) were observed in 30 (16%). No patients died within 30 days of surgery. The incidence of severe complications was 3.6% in patients with mFI of 0, 16.2% in patients with mFI of 1, 23.4% in patients with mFI of 2, and 31.6% in patients with mFI of 3 or more, and was correlated with the grade of mFI. Univariate and multivariate analyses showed that the high mFI was significantly predictive of postoperative complications. Frail patients of mFI ≥ 2 were at 3.0-fold greater risk of severe complications than non-frail patients of mFI 0 or 1. CONCLUSION: mFI was associated with morbidity after lung cancer surgery. Preoperative frailty assessment and appropriate intervention to frail patients would be required to improve postoperative outcomes.

Improvement of Lithium-Sulfur Battery Performance by Porous Carbon Selection and LiFSI/DME Electrolyte Optimization.

High-concentration lithium bis(fluorosulfonyl)imide/1,2-dimethoxyethane (LiFSI/DME) electrolytes are promising candidates for highly reversible lithium-metal anodes. However, the performance of lithium-sulfur (Li-S) batteries with a high concentration of LiFSI/DME declines because LiFSI reacts irreversibly with lithium polysulfide, which is formed during the charge-discharge process of Li-S batteries. Hence, to apply high-concentration LiFSI/DME to Li-S batteries, we investigated carbon with an appropriate pore size for use in a sulfur composite cathode and optimized the composition of high-concentration LiFSI/DME. The results showed that the combination of carbon with mesopores of 2-3 nm diameter and 3 M LiFSI in DME/1,1,2,2-tetrafluoroethyl 2,2,3,3-tetrafluoropropylether (HFE) (1:1 by vol.) provided a high-rate capability (943 mA h g-1 at a rate of 2 C). Moreover, the ratio of the 50th discharge capacity to the 2nd discharge capacity (capacity retention) improved from 50.0 to 61.6% with HFE dilution of high-concentration LiFSI/DME. The improved performance was achieved by suppressing the dissolution of lithium polysulfide, decreasing the viscosity of the electrolyte, and forming a thin solid electrolyte interface on the lithium-metal anode due to HFE dilution.

Predicting pathological highly invasive lung cancer from preoperative [18F]FDG PET/CT with multiple machine learning models.

PURPOSE: The efficacy of sublobar resection of primary lung cancer have been proven in recent years. However, sublobar resection for highly invasive lung cancer increases local recurrence. We developed and validated multiple machine learning models predicting pathological invasiveness of lung cancer based on preoperative [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) radiomic features. METHODS: Overall, 873 patients who underwent lobectomy or segmentectomy for primary lung cancer were enrolled. Radiomics features were extracted from preoperative PET/CT images with the PyRadiomics package. Seven machine learning models and an ensemble of all models (ENS) were evaluated after 100 iterations. In addition, the probability of highly invasive lung cancer was calculated in a nested cross-validation to assess the calibration plot and clinical usefulness and to compare to consolidation tumour ratio (CTR) on CT images, one of the generally used diagnostic criteria. RESULTS: In the training set, when PET and CT features were combined, all models achieved an area under the curve (AUC) of ≥ 0.880. In the test set, ENS showed the highest mean AUC of 0.880 and smallest standard deviation of 0.0165, and when the cutoff was 0.5, accuracy of 0.804, F1 of 0.851, precision of 0.821, and recall of 0.885. In the nested cross-validation, the AUC of 0.882 (95% CI: 0.860-0.905) showed a high discriminative ability, and the calibration plot indicated consistency with a Brier score of 0.131. A decision curve analysis showed that the ENS was valid with a threshold probability ranging from 3 to 98%. Accuracy showed an improvement of more than 8% over the CTR. CONCLUSION: The machine learning model based on preoperative [18F]FDG PET/CT images was able to predict pathological highly invasive lung cancer with high discriminative ability and stability. The calibration plot showed good consistency, suggesting its usefulness in quantitative risk assessment.

Age estimation using methylation-sensitive high-resolution melting (MS-HRM) in both healthy felines and those with chronic kidney disease.

Age is an important ecological tool in wildlife conservation. However, it is difficult to estimate in most animals, including felines-most of whom are endangered. Here, we developed the first DNA methylation-based age-estimation technique-as an alternative to current age-estimation methods-for two feline species that share a relatively long genetic distance with each other: domestic cat (Felis catus; 79 blood samples) and an endangered Panthera, the snow leopard (Panthera uncia; 11 blood samples). We measured the methylation rates of two gene regions using methylation-sensitive high-resolution melting (MS-HRM). Domestic cat age was estimated with a mean absolute deviation (MAD) of 3.83 years. Health conditions influenced accuracy of the model. Specifically, the models built on cats with chronic kidney disease (CKD) had lower accuracy than those built on healthy cats. The snow leopard-specific model (i.e. the model that resets the model settings for snow leopards) had a better accuracy (MAD = 2.10 years) than that obtained on using the domestic cat model directly. This implies that our markers could be utilised across species, although changing the model settings when targeting different species could lead to better estimation accuracy. The snow leopard-specific model also successfully distinguished between sexually immature and mature individuals.

The relationship between plant-eating and hair evacuation in snow leopards (Panthera uncia).

Although most felids have an exclusive carnivore diet, the presence of plant matter in scat has been reported among various species. This indicates that there may be an adaptive significance to the conservation of plant-eating behavior in felid evolution. Some studies have hypothesized that felids consume plants for self-medication or as a source of nutrition. In addition, it is thought that plant intake helps them to excrete hairballs, however, no scientific work has confirmed these effects. Thus, the objective of this study is to investigate the relationship between plant intake and hair evacuation in felid species. We selected snow leopards (Panthera uncia) as the study species because they have longer and denser hair than other felids. The behavior of 11 captive snow leopards was observed and scat samples from eight of them and two other captive individuals were analyzed. Snow leopards evacuate hair possibly by vomiting and excreting in scats. The frequency of plant-eating and vomiting and the amount of hair and plant in scat were evaluated. We found that the frequency of vomiting was much lower than the frequency of plant-eating. In addition, there was no significant relationship between the amount of plant matter contained in scats and the amount of hair in scats. Contrary to the common assumption, our results indicate that plant intake has little effect on hair evacuation in felid species.

Operando soft X-ray absorption spectroscopic study on microporous carbon-supported sulfur cathodes.

Sulfur is a promising material for next-generation cathodes, owing to its high energy and low cost. However, sulfur cathodes have the disadvantage of serious cyclability issues due to the dissolution of polysulfides that form as intermediate products during discharge/charge cycling. Filling sulfur into the micropores of porous carbon is an effective method to suppress its dissolution. Although microporous carbon-supported sulfur cathodes show an electrochemical behavior different from that of the conventional sulfur ones, the corresponding reaction mechanism is not clearly understood. In this study, we focused on clarifying the reaction mechanism of microporous carbon-supported sulfur cathodes by operando soft X-ray absorption spectroscopy. In the microporous carbon support, sulfur was present as smaller fragments compared to conventional sulfur. During the first discharge process, the sulfur species in the microporous carbon were initially reduced to S6 2- and S2 2- and then to Li2S. The S6 2- and S2 2- species were observed first, with S2 2- being the main polysulfide species during the discharge process, while Li2S was produced in the final discharge process. The narrow pores of microporous carbon prevent the dissolution of polysulfides and influence the reaction mechanism of sulfur cathodes.

A surgical case of synchronous solitary splenic metastasis from lung squamous cell carcinoma: report of a case and review of the literature.

Solitary splenic metastasis is an extremely rare event. We herein report a surgical case of a solitary splenic metastasis from lung cancer. A 78-year-old man presented with abdominal pain. Abdominal computed tomography (CT) showed splenic rupture. Coil embolization to the splenic artery was performed, and the patient's condition improved. Chest CT showed a 5-cm lung mass in the right upper lobe, suggesting lung cancer with splenic metastasis. Transbronchial aspiration cytology showed squamous cell carcinoma of the lung. We diagnosed the patient with lung cancer (cT2bN0M1b [spleen only] stage IVA) and performed splenectomy and right upper lobectomy separately. Both lesions were squamous cell carcinoma and positive for p40. Thus, primary lung squamous cell carcinoma and solitary splenic metastasis were diagnosed. The patient was still alive without recurrence 15 months postoperatively. We herein report a rare case of lung squamous cell carcinoma with solitary splenic metastasis and review the literature.

A case of primary pulmonary leiomyosarcoma completely resected after neoadjuvant chemotherapy.

BACKGROUND: Primary pulmonary leiomyosarcoma is a rare malignant tumor. We herein report a case of primary pulmonary leiomyosarcoma that was completely resected by surgery after neoadjuvant chemotherapy. CASE PRESENTATION: A 60-year-old man presented with cough. Chest computed tomography showed an 11-cm mass in the right upper lobe of the lung that had invaded the superior vena cava. Endobronchial ultrasound-guided transbronchial needle aspiration revealed leiomyosarcoma of the lung. We considered complete resection of the tumor to be very difficult because of the tumor invasion into the right atrium inflow of the superior vena cava, so we performed chemotherapy using doxorubicin for five cycles. After chemotherapy, the tumor size decreased to 5.6 cm, and we performed right upper lobectomy with combined resection of the superior vena cava. The tumor was completely resected by surgery. The patient is alive without recurrence 17 months postoperatively. CONCLUSIONS: We encountered a case of primary pulmonary leiomyosarcoma that was successfully treated by surgery after neoadjuvant chemotherapy. Doxorubicin monotherapy was effective in this case. Surgery combined with neoadjuvant chemotherapy should be considered for such cases, as a long-term survival can be achieved by complete resection of primary pulmonary leiomyosarcoma.

A strategy for pulmonary resection after contralateral diaphragm plication: a surgical case report.

BACKGROUND: Pulmonary carcinoma patients with low pulmonary function cannot be treated surgically because of the high risk of complications. Diaphragmatic eventration is a disease characterized by diaphragmatic paralysis and dyspnea. Here, we report a surgical case of multiple pulmonary carcinomas with contralateral diaphragmatic eventration. CASE PRESENTATION: The patient was a 75-year-old woman with multiple metachronous right lung carcinomas complicated by left diaphragmatic eventration. When she was 70 years old, a right upper lobectomy and right S6b wedge resection were performed for double lung carcinomas. Five years later, two new lung tumors in her right lower lobe and left diaphragmatic eventration were identified, but resection was thought to be impossible because of her low pulmonary function. We performed video-assisted thoracoscopic surgery (VATS) plication with carbon dioxide (CO2) insufflation for the left diaphragmatic eventration, and her pulmonary function improved. Subsequently, we performed a right S6 wedge resection and right S9 segmentectomy for the double lung tumors with no complications. The tumors were diagnosed as double primary carcinomas. CONCLUSIONS: Our case presented with low pulmonary function and right multiple lung carcinomas with left diaphragmatic eventration. VATS plication for the left diaphragmatic eventration achieved improvement in her pulmonary function, and right pulmonary resection for the lung carcinomas was performed. VATS plication can expand the choice of treatments in such cases.

Randomized controlled phase III trial of adjuvant chemoimmunotherapy with activated cytotoxic T cells and dendritic cells from regional lymph nodes of patients with lung cancer.

Randomized controlled trial of adjuvant chemoimmunotherapy for lung cancer indicated a significant advantage in patients receiving immunotherapy. Herein we report the final results and immunological analysis with a median follow-up of 59.6 months. Patients with post-surgical lung cancer were randomly designated to receive either chemoimmunotherapy (group A, immunotherapy arm) or chemotherapy (group B, control arm). The immunotherapy comprised the adoptive transfer of autologous activated killer T cells and dendritic cells (AKT-DC). The 2- and 5-year overall survival (OS) rates were 96.0 and 69.4% in group A and 64.7 and 45.1% in group B, respectively. Multivariate analysis results revealed that the hazard ratio was 0.439. The 2- and 5-year recurrence-free survival rates were 70.0 and 57.9% in group A and 43.1 and 31.4% in group B, respectively. Subgroup analysis for the OS between treatment groups indicated that younger patients (≤ 55 years: HR 0.098), males (HR 0.474), patients with adenocarcinoma (HR 0.479), patients with stage III cancer (HR 0.399), and those who did not receive preoperative chemotherapy (HR 0.483) had lower HRs than those in the other groups. Immunological analysis of cell surface markers in regional lymph nodes of subjects receiving immunotherapy indicated that the CD8+/CD4+ T-cell ratio was elevated in survivors. Patients with non-small-cell lung cancer benefited from adoptive cellular immunotherapy as an adjuvant to surgery. Patients with stage III cancer, those with adenocarcinoma, and those not receiving preoperative chemotherapy were good candidates. Lastly, cytotoxic T cells were important for a favorable chemoimmunotherapy outcome.

Differential diagnosis of primary intrapulmonary thymoma: a report of two cases.

Primary intrapulmonary thymomas (PITs), which are intrapulmonary tumors without an associated mediastinal component, are very rare. The diagnosis of a PIT can be difficult. Here, we report two cases of resected PITs that were difficult to differentiate from other lung tumors. The patients, of a 62-year-old man and a 64-year-old woman, had no significant symptoms and were both referred to our hospital due to the presence of an abnormal shadow on chest computed tomography (CT). The patients underwent (18)F-fluorodeoxyglucose positron emission tomography-CT (FDG-PET/CT) and subsequently tumor excision. A PIT was confirmed histopathologically in the surgical specimens from both patients. In one case, the tumor consisted of a type A thymoma without abnormal FDG uptake. In the other case, the tumor consisted of a type B2 thymoma presenting with weak FDG uptake. This report thus documents two cases of PITs with different histopathologic and FDG-PET/CT findings. Thoracoscopic surgery is essential in the differential diagnosis between PITs and other lung tumors.

Randomized controlled phase III trial of adjuvant chemo-immunotherapy with activated killer T cells and dendritic cells in patients with resected primary lung cancer.

PURPOSE: We conducted a phase III randomized controlled trial (RCT) to investigate the efficacy of postsurgical adjuvant immunotherapy combined with chemotherapy. The immunotherapy targets were residual micrometastases and clones resistant to chemotherapy. PATIENTS AND METHODS: Between April 2007 and July 2012, 103 postsurgical non-small cell lung cancer patients were randomly assigned to receive either chemo-immunotherapy (group A) or chemotherapy (group B). The immunotherapy consisted of the adoptive transfer of autologous activated killer T cells and dendritic cells obtained from the lung cancer patients' own regional lymph nodes. RESULTS: The 2-year overall survival rates in groups A and B were 93.4 and 66.0 %, and the 5-year rates were 81.4 and 48.3 %, respectively. The differences were statistically significantly better in group A. The hazard ratio (HR) was 0.229 (p = 0.0013). The 2- and 5-year recurrence-free survival rates were 68.5, 41.4 and 56.8, 26.2 % in groups A and B, respectively. Those differences were also statistically significant (log-rank test p = 0.0020). The HR was 0.423 (p = 0.0027) in favor of group A. As for adverse reactions to immunotherapy, of a total of 762 courses, 52 (6.8 %) were accompanied with chills and shivering, and 47 (6.2 %), with fever (>38 °C). CONCLUSIONS: Immunotherapy has the potential to improve the postsurgical prognosis of lung cancer patients, but a large-scale multi-institutional RCT is awaited for further confirmation of this study.

ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity.

BACKGROUND: Anaplastic lymphoma kinase (ALK) fusion gene-positive lung cancer accounts for 4-5% of non-small cell lung carcinoma. A clinical trial of the specific inhibitor of ALK fusion-type tyrosine kinase is currently under way. METHODS: ALK fusion gene products were analyzed immunohistochemically with the materials obtained by surgery or by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The echinoderm microtubule-associated protein-like 4(EML4)-ALK or kinesin family member 5B (KIF5B)-ALK translocation was confirmed by the reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). After eligibility criteria were met and informed consent was obtained, 3 patients were enrolled for the Pfizer Study of Crizotinib (PF02341066), Clinical Trial A8081001, conducted at Seoul National University. RESULTS: Out of 404 cases, there were 14 of EML4-ALK non-small cell carcinoma (NSCLC) and one KIF5B-ALK NSCLC case (8 men, 7 women; mean age, 61.9 years, range 48-82). Except for 2 light smokers, all patients were non-smokers. All cases were of adenocarcinoma with papillary or acinar subtypes. Three were of stage IA, 5 of stage IIIA, 1 of stage IIIB and 6 of stage IV. Ten patients underwent thoracotomy, 3 received chemotherapy and 2 only best supportive care (BSC). One BSC and 2 chemotherapy cases were enrolled for the clinical trial. Patients with advanced stages who received chemotherapy or best supportive care were younger (54.0±6.3) than those who were surgically treated (65.8±10.1) (p<0.05). The powerful effect of ALK inhibitor on EML4-ALK NSCLC was observed. Soon after its administration, almost all the multiple bone and lymph node metastases quickly disappeared. Nausea, diarrhea and the persistence of a light image were the main side effects, but they diminished within a few months. CONCLUSION: ALK-fusion gene was found in 3.7% (15/404) NSCLC cases and advanced disease with this fusion gene was correlated with younger generation. The ALK inhibitor presented in this study is effective in EML4-ALK NSCLC cases. A further study will be necessary to evaluate the clinical effectiveness of this drug.

Is there a role for pulmonary metastasectomy with a curative intent in patients with metastatic urinary transitional cell carcinoma?

BACKGROUND: Systemic chemotherapy remains the standard treatment for metastatic transitional cell carcinoma (TCC) of the urinary tract. For pulmonary metastases of several malignancies, surgical therapy for selected patients has become a treatment of choice to achieve cure. However, data on pulmonary metastasectomy for urinary TCC remain limited. METHODS: From 1990 to 2005, 2,288 patients who underwent pulmonary metastasectomy for all types of malignancy were registered in the Metastatic Lung Tumor Study Group of Japan. Of these, we extracted 32 patients with TCC who underwent pulmonary metastasectomy with a curative intent from the database. We investigated the surgical outcomes of the patients, focusing on long-term progression-free survival (PFS) and modified PFS as a parameter for achieving a cure. In modified PFS, when the disease-free status had continued for longer than two years after repeated resection at the last follow-up, the first recurrence was not considered as an event. RESULTS: The five-year overall survival and PFS rates were 50% and 26%, respectively. Including 3 patients who underwent a second pulmonary metastasectomy for recurrence, 9 patients survived without recurrence for more than 5 years, resulting in a modified five-year PFS rate of 40%. Multivariate analysis revealed that a pulmonary metastasis greater than 3 cm was a significantly poor prognostic factor. The modified five-year PFS rate for patients with a pulmonary metastasis smaller than 3 cm in diameter was 65%. CONCLUSIONS: Pulmonary metastasectomy may have a curative role in the treatment of metastatic TCC in appropriately selected patients, especially those with a small solitary pulmonary metastasis.

Detection of epithelial growth factor receptor mutations in cerebrospinal fluid from patients with lung adenocarcinoma suspected of neoplastic meningitis.

BACKGROUND: Neoplastic meningitis (NM) is a devastating neurological complication of cancer that needs to be diagnosed in the early stages of disease. Polymerase chain reaction detection of epithelial growth factor receptor (EGFR) mutations in cerebrospinal fluid (CSF), which are predictive markers for EGFR tyrosine kinase inhibitor therapy in lung cancer, might be important to diagnose and to treat NM in patients with lung cancer. In this study, we attempted to detect EGFR mutations in CSF and to compare EGFR status between CSF and primary or metastatic lesions in patients with lung adenocarcinoma suspected of NM. METHODS: Twenty-nine patients with lung adenocarcinoma suspected of having NM underwent lumbar puncture. EGFR status of CSF was analyzed by direct DNA sequencing. EGFR mutations of primary or metastatic lesions (lymph nodes and bones) were analyzed in 20 cases. RESULTS: EGFR mutations were detected in CSF of 13 (45%) of 29 patients. In 5 (31%) of 16 patients with negative CSF cytology, EGFR mutations were detected. In four patients, EGFR mutations were shown in CSF, but not in primary or metastatic lesions. Conversely, in two patients, EGFR mutations were shown in primary or metastatic lesions, but not in CSF despite positive CSF cytology. CONCLUSIONS: EGFR mutations, suggesting the existence of malignant cells, were detected in CSF, even in patients with non-small cell lung cancer with negative cytological results. EGFR mutations in CSF do not always reflect the same status as in primary or metastatic lesions.

Comparison of 21-gauge and 22-gauge aspiration needle during endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has typically been performed using the 22 gauge (G) dedicated TBNA needle. Recently a new 21G TBNA needle has been introduced. The efficacy of using a larger gauge biopsy needle during EBUS-TBNA has not been reported. The purpose of this study was to compare the diagnostic yield and utility of 21G and 22G needles during EBUS-TBNA. METHODS: EBUS-TBNA was performed using both 21G and 22G needles. Cytological and histological findings were recorded for each samples obtained by an independent cytologist and pathologist. The cellularity and blood contamination were evaluated in the cytological samples. The quality of the histological core was evaluated by the amount of blood clots versus the actual tissue. Each factor was compared within two slides from the two different size needles. The diagnostic yield and the differences of the cytology and histology were analysed. RESULTS: The evaluation of 45 lesions by EBUS-TBNA revealed that tumour cells were equally detected by both 21G and 22G needles. Two patients of adenocarcinoma were histologically diagnosed only by the 21G needle. Although histological structure was better preserved in five lesions collected by the 21G needle, there was more blood contamination with the 21G needle (P < 0.0001). CONCLUSIONS: There were no differences in the diagnostic yield between the 21G and 22G needles during EBUS-TBNA. The preserved histological structure of the samples obtained by the 21G needle may be useful for the diagnosis of mediastinal and hilar adenopathy of unknown aetiology which may be a challenge with the 22G needle.

Successfully treated postbronchoplasty bronchial stenosis using short-interval repeated endobronchial balloon dilation.

A 63-year-old man with a history of lung cancer underwent lobectomy of the right upper lobe and bronchoplasty. At the 2-month follow-up, bronchial stenosis due to a granuloma was observed. Endoscopic débridement and balloon dilation were performed. At 1 month after the dilation, atelectasis occurred owing to cicatricial stenosis. We repeated balloon dilation, but the patient suffered from cicatricial restenosis. After a failed stent placement, balloon dilation was then performed every 2 weeks under local anesthesia; the stenosis was resolved after performing dilation 7 times. Short-term repeated balloon dilation was effective in this case.

Production of both IL-27 and IFN-gamma after the treatment with a ligand for invariant NK T cells is responsible for the suppression of Th2 response and allergic inflammation in a mouse experimental asthma model.

Using an allergen-induced airway inflammation model, we show that an injection of alpha-galactosylceramide (alpha-GalCer), a ligand for invariant NK T (iNKT) cells, induced IL-27 and that this process is essential for the attenuation of the Th2 response. After the systemic administration of alpha-GalCer into the mice primed with OVA in alum, Th2 cytokine production of OVA-primed CD4(+) T cells in their lymph nodes, IgG1 and IgE Ab formation, and infiltration of eosinophils in bronchoalveolar lavage after the OVA challenge were suppressed. Systemic administration of rIFN-gamma into OVA-primed mice could not reproduce these effects of alpha-GalCer. IL-27p28 was detected both in the culture supernatant of alpha-GalCer-stimulated spleen cells and in the serum of the alpha-GalCer-treated mice, but not in the iNKT cell-deficient mice. Splenic iNKT cells produced IL-27p28 in the culture supernatant upon stimulation with PMA plus ionomycin, although the transcript of IL-27p28 in the iNKT cells was constitutively expressed regardless of the stimulation. By contrast, the transcript of IL-27EBI3 was induced in the iNKT cells upon stimulation with PMA plus ionomycin in vitro and with alpha-GalCer treatment in vivo, suggesting that IL-27 (p28/EBI3) could be produced by iNKT cells in an activation-dependent manner. Although repeated injections of rIL-27 did not substitute for the effects of a single injection of alpha-GalCer, administration of rIL-27 along with rIFN-gamma reproduced in vivo effects of the alpha-GalCer injection. These data indicate that production of both IL-27 and IFN-gamma by the alpha-GalCer treatment is responsible for suppression of the Th2 response and allergic inflammation.