Effects of Cytokines on Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL).@*METHODS@#Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits.@*RESULTS@#It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated.@*CONCLUSION@#Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.

Endotoxin Is Not Essential for the Development of Cockroach Induced Allergic Airway Inflammation

PURPOSE: Cockroach (CR) is an important inhalant allergen and can induce allergic asthma. However, the mechanism by which CR induces airway allergic inflammation and the role of endotoxin in CR extract are not clearly understood in regards to the development of airway inflammation. In this study, we evaluated whether endotoxin is essential to the development of CR induced airway allergic inflammation in mice. MATERIALS AND METHODS: Airway allergic inflammation was induced by intranasal administration of either CR extract, CR with additional endotoxin, or endotoxin depleted CR extract, respectively, in BALB/c wild type mice. CR induced inflammation was also evaluated with toll like receptor-4 (TLR-4) mutant (C3H/HeJ) and wild type (C3H/HeN) mice. RESULTS: Intranasal administration of CR extracts significantly induced airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation, as well as goblet cell hyperplasia in a dose-dependent manner. The addition of endotoxin along with CR allergen attenuated eosinophilic inflammation, interleukin (IL)-13 level, and goblet cell hyperplasia of respiratory epithelium; however, it did not affect the development of AHR. Endotoxin depletion in CR extract did not attenuate eosinophilic inflammation and lymphocytosis in BAL fluid, AHR and IL-13 expression in the lungs compared to CR alone. The attenuation of AHR, eosinophilic inflammation, and goblet cell hyperplasia induced by CR extract alone was not different between TLR-4 mutant and the wild type mice. In addition, heat inactivated CR extract administration induced attenuated AHR and eosinophilic inflammation. CONCLUSION: Endotoxin in CR extracts may not be essential to the development of airway inflammation.

Protease-Activated Receptor 2 Is Involved in Th2 Responses against Trichinella spiralis Infection

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.

The Soluble Tumor Necrosis Factor-Alpha Receptor Suppresses Airway Inflammation in a Murine Model of Acute Asthma

PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. TNF-alpha blocking strategies are now being tried in asthma patients. This study investigated whether TNF-alpha blocking therapy inhibits airway inflammation and airway hyperresponsiveness (AHR) in a mouse model of asthma. We also evaluated the effect of TNF-alpha blocking therapy on cytokine production and adhesion molecule expression. MATERIALS AND METHODS: Ovalbumin (OVA) sensitized BALB/c female mice were exposed to intranasal OVA administration on days 31, 33, 35, and 37. Mice were treated intraperitoneally with soluble TNF-alpha receptor (sTNFR) during the OVA challenge. RESULTS: There were statistically significant decreases in the numbers of total cell and eosinophil in bronchoalveolar lavage fluid (BALF) in the sTNFR treated group compared with the OVA group. However, sTNFR-treatment did not significantly decrease AHR. Anti-inflammatory effect of sTNFR was accompanied with reduction of T helper 2 cytokine levels including interleukin (IL)-4, IL-5 and IL-13 in BALF and vascular cell adhesion molecule 1 expression in lung tissue. CONCLUSION: These results suggest that sTNFR treatment can suppress the airway inflammation via regulation of Th2 cytokine production and adhesion molecule expression in bronchial asthma.

The Effect of Rush Immunotherapy with House Dust Mite in the Production of IL-5 and IFN-gamma from the Peripheral Blood T Cells of Asthmatic Children

Although the mechanisms are unclear, rush immunotherapy (RIT) may be effective to treat allergic diseases. We investigated the long-term modifications of cellular immunity as a mechanism of RIT. The RIT group, included 15 house dust mite (HDM)-sensitized asthmatic children, received RIT only with Dermatophagoides farinae (Der f) and Dermatophagoides pteronyssinus (Der p), whereas the control group, consisted of 10 HDM-sensitized asthmatic children, did not receive RIT. The asthma symptom scores and the skin reactivities to Der f were measured. The cellular proliferative responses and intracellular interleukin (IL)-5 and interferon (IFN)-gamma productions from peripheral blood T cells were also measured before, 8 weeks and 1 yr after RIT. The symptom scores, skin reactivity to Der f and cellular proliferative responses to Der f were decreased significantly after 8 weeks and maintained until 1 yr of RIT. The IFN-gamma/IL-5 ratio of the CD3(+) and CD4(+) cells were increased significantly after 8 weeks and maintained until 1 yr of RIT, while there were no changes in the control group. These data indicate that the continuous functional modification from Th2 to Th1 phenotype of the CD4(+) T cells are developed after RIT in the asthmatic children sensitized with HDM.

Glycoproteomic analysis of plasma from patients with atopic dermatitis: CD5L and ApoE as potential biomarkers

Atopic dermatitis (AD) is an inflammatory skin disorder that is both uncomfortable and distressing to patients, and its prevalence has been steadily increasing. It is obvious that the identification of efficient markers of AD in plasma would offer the possibility of effective diagnosis, prevention, and treatment strategies. In this study, a proteomic approach was used to analyze plasma glycoproteins from both children with AD and healthy child donors. Several protein spots showing significant quantitative changes in the AD patients were identified. Through sequential studies, it was confirmed that CD5L and ApoE were significantly up-regulated or down-regulated, respectively, in the plasma from AD patients compared with that from healthy donors. In addition, we suggest that the up-regulated CD5L in AD patients causes eosinophilia by inhibiting apoptosis or promoting the proliferation of eosinophils either in combination with or without IL-5. The glycoproteomic data in this study provides clues to understanding the mechanism of atopic alterations in plasma and suggests AD-related proteins can be used as candidate markers for AD.

The Role of Cyclosporine and Mycophenolate in an Orthotopic Porcine-to-Rat Corneal Xenotransplantation

We performed this study to investigate the feature of rejection in porcine-to-rat corneal orthotopic transplantation and to evaluate the effect of cyclosporine and mycophenolate on the xeno-rejection. Orthotopic corneal transplantation was done at 91 Sprague-Dawley rats, and they were divided into 10 groups based on the combination of immunosuppressants including dexamethasone, cyclosporine, and mycophenolate mofetil. Graft survival was analyzed and grafted eyes were examined with Hematoxylin & Eosin and CD4 or CD8 staining. Enzyme-linked immunosorbent assays were done for interleukin-2 (IL-2), IL-4, IL-5, IL-10, and interferon (IFN)-gamma in cornea, lacrimal gland, and cervical lymph nodes. The longest median survival of the immune suppressant group was 11.00+/-1.96 days, which showed no statistical differences compared with that of control (8.00+/-1.52 days). The neutrophils were prominent in the early phase but soon gave way to the monocytes. The number of CD8+ cells was higher than that of CD4+ cells. IL-2 and IFN-gamma markedly increased at 10 to13 days in cornea, lacrimal glands, and cervical lymph nodes, which showed a decrease with immunosuppressants except in the cornea. In conclusion, cyclosporine and mycophenolate could not prevent the rejection in porcine to rat orthotopic corneal xenograft associated with infiltraton of CD8+ and innate immune cells.

Effects of prednisolone on eosinophils, IL-5, eosinophil cationic protein, EG2+ eosinophils, and nitric oxide metabolites in the sputum of patients with exacerbated asthma

Corticosteroids are considered to be one of the most effective medicine for asthma by suppressing airway inflammation. This study was carried out to investigate the effects of prednisolone in the sputum of exacerbated asthmatics. Clinical severity, cell differentials, levels of interleukin (IL)-5, eosinophil cationic protein (ECP), EG2+ eosinophils, and nitric oxide (NO) metabolites were measured. Sputum was examined 2 weeks apart in 13 exacerbated asthmatics before and after prednisolone treatment, and once in 12 stable asthmatics. We used a sandwich ELISA for IL-5, fluoroimmunoassay for ECP, immunohistochemical staining for EG2+ eosinophils, a NO metabolites assay using modified Griess reaction. Exacerbated asthmatics, in comparison with stable asthmatics, had significantly higher proportion of eosinophils, higher level of ECP, higher percentage of EG2+ eosinophils, and NO metabolites. Exacerbated asthmatics after treatment with prednisolone had reduced the proportions of eosinophils, reduced level of IL-5, ECP and percentage of EG2+ eosinophils. FEV1 was correlated with the proportion of eosinophils, ECP, and IL-5 respectively. These findings suggest that prednisolone is considered to be effective medicine for asthma by suppressing eosinophil activation through IL-5.