Tim-3 facilitates immune escape in benzene-induced acute myeloid leukemia mouse model by promoting macrophage M2 polarization.

Benzene poisoning can cause acute myeloid leukemia (AML) through a variety of passways. Tim-3 has gained prominence as a potential candidate in mediating immunosuppression in tumor microenvironments. The macrophage polarization is also related to immune escape. Herein, we reported that Tim-3 and macrophage M2 polarization play a vital role in benzene-induced AML. First, the benzene-induced AML C3H/He mouse model was constructed by subcutaneously injecting 250 mg/kg of benzene. After six months, macrophage phenotype, cytokines, and Tim-3 expression levels were investigated. Flow cytometry assay revealed that the T-cell inhibitory receptor Tim-3 was significantly upregulated in both bone marrow and spleen of the benzene-induced AML mouse model. Elisa's results displayed a decreased serum level of IL-12 while increased TGF-ß1. Mechanistically, changes in cytokine secretion promote the growth of M2-type macrophages in the bone marrow and spleen, as determined by immunofluorescence assay. The increased levels of PI3K, AKT, and mTOR in the benzene-exposure group further proved the crucial role of Tim-3 in regulating the functional status of macrophages in the AML microenvironment. These results demonstrate that Tim-3 and macrophage polarization may play a vital role during the immune escape of the benzene-induced AML. This study provides a new potential intervention site for immune checkpoint-based AML therapeutic strategy.

[Clinical observation of rheumatoid arthritis associated interstitial lung disease patients and changes of serum cytokines thereof].

OBJECTIVE: To observe the clinical feature of rheumatoid arthritis associated interstitial lung disease (RA-ILD) patients and changes of serum cytokines tumor growth factor (TGF)-beta 1, tumor necrosis factor (TNF)-alpha, insulin-like growth factor (IGF)-1, and platelet derived growth factor (PDGF)-AB. METHODS: The clinical manifestations, lung high resolution CT (HRCT), lung functions, blood gas and other relative laboratory findings of 30 RA-ILD patients and 35 RA patients were observed. ELISA was used to detect the levels of TGF-beta 1, TNF-alpha, IGF-1, and PDGF-AB. Thirty healthy volunteers were observed too as controls. RESULTS: The clinical manifestations of RA-ILD patients were more serious than those of the RA patients. The ESR was faster, the serum C-reactive protein, rheumatoid factor (RF), and globulin levels higher, and pulmonary arterial pressure higher too in the RA-ILD patients than in the RA patients (all P<0.01). The main respiratory manifestations of the RA-ILD patients were cough, expectoration, chest distress, short breath, chest pain, change of breath sounds, Velcro râles, and dyspnea. The main lung HRCT findings included thickening of interlobular septum and bronchial wall, pachynsis pleurae, mosaic sign, bronchiectasis, emphysema, patching shadow, honeycombing, fibrous scar, etc. Pulmonary function test showed that the levels of vital capacity, forced vital capacity, maximum midexpiratory flow, and diffusing capacity of the lung for carbon monoxide of the RA-ILD patients were all significantly lower than those of the RA patients (all P<0.01). Arterial gas test showed that the PO2 of the RA-ILD patients was significantly lower than that of the RA patients (P<0.01). The TGF-beta 1; TNF-alpha, IGF-1, and PDGF-AB of both the RA-ILD and RA patients were all significantly higher than those of the healthy volunteers (all P<0.01), and the levels of these cytokines of the RA-ILD patients were all higher than those of the RA patients (all P<0.01). CONCLUSION: The symptoms and signs of the RA-ILD patients are more serious, the lung HRCT changes more obvious, lung function decreases, and the levels of TGF-beta 1, TNF-alpha, IGF-1, and PDGF-AB increase.

[Clinical study on treatment of acute paraquat poisoning].

OBJECTIVE: To investigate the clinical therapeutic effect of methylprednisolone combined with cyclophosphamide and Etanercept method on acute paraquat poisoning. METHODS: 136 patients with acute paraquat poisoning were divided into the normal therapy group and the intensive therapy group randomly. Methylprednisolone, cyclophosphamide and Etanercept were used in the intensive therapy group. Methylprednisolone 500 mg was given intravenously per day for continuous three days followed by 200 mg intravenous per day. Then methylprednisolone was decreased gradually 14 d or 21 d later according to the patient's condition. Cyclophosphamide 600 mg was given intravenously twice weekly for 2 weeks and Etanercept 25 mg was given hypodermic injection twice weekly for 3 weeks. Curative effect evaluation was done at 7, 14, 21 d and 12 weeks after therapy. RESULTS: The survival rate of the intensive therapy group was obviously higher than that of the normal therapy group (P<0.01) on 7, 4, 21 d and 12 weeks. The cure rate of the intensive group were 94.6% (intake dose<50 ml 20% paraquat solution), 75.0% (intake dose 50 approximately 100 ml 20% paraquat solution), 12.5% (intake dose>100 ml 20% paraquat solution) respectively, while the cure rate of the normal group were 16.7% (intake dose<50 ml 20% paraquat solution), 8.3% (intake dose 50 approximately 100 ml 20% paraquat solution), 0% (intake dose>100 ml 20% paraquat solution) respectively. The total cure rate of the intensive therapy group (78.3%) 12 weeks later was higher than that of the normal group (11.9%). CONCLUSION: Methylprednisolone combined with cyclophosphamide and Etanercept intensive therapy has the curative effect on acute paraquat poisoning.