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.
Humans ; Leukemia, Promyelocytic, Acute/diagnosis* ; Cytokines/metabolism* ; Interleukin-10 ; Interleukin-17/metabolism* ; Interleukin-6/metabolism* ; Interleukin-5/metabolism* ; Blood Coagulation Disorders ; Ferritins ; Tretinoin

OBJECTIVE: To study the expression of intedeukin-5 (IL-5) mRNA and protein in Nasal polyps and in the inferior turbinate, and to explore the relationship between the expression and the Clinical features. METHOD: Real time fluorescent quantitative PCR(RT-qPCR) and immunohistochemical staining were used to detect the expression of intedeukin-5 (IL-5) mRNA and protein in nasal polyps of 24 cases and in inferior turbinate of 15 cases. RESULT: The expression of IL-5 mRNA in Nasal polyps was 7.52 times higher than that in the inferior turbinate (P < 0.01). The expression rate of IL-5 protein in Nasal polyps was 79.17%, significantly higher than that in the inferior turbinate (26.67%) (chi2 = 10.52, P < 0.01). The differece of expression of IL-5 mRNA was not associated with the sexual distinction, unilateral or bilateral nasal polyps and primary or recurrent nasal polyps (P > 0.01), but was associated with the single or multiple nasal polyps, nasal polyps with or without allergic rhinitis and/or asthma. The differece of expression of IL-5 protein was not associated with the sexual distinction, unilateral or bilateral nasal polyps, primary or recurrent nasal polyps, nasal polyps with or without allergic rhinitis and/or asthma, but was associated with the single and multiple nasal polyps. CONCLUSION The high expression of IL-5 mRNA and protein is closely related with the formation edema and development of nasal polyps. Some clinical features of Nasal polyps related to the expression level of IL-5 in nasal polyps.
Female ; Humans ; Interleukin-5 ; genetics ; metabolism ; Male ; Nasal Polyps ; metabolism ; RNA, Messenger ; genetics ; Turbinates ; metabolism

OBJECTIVE: To explore the relationship of the expression of thymic stromal lymphopoietin (TSLP) in nasal polyps tissues and the Th2 inflammatory response. METHOD: Sixty patients with nasal polyps were collect ed. The immunohistochemical staining method was used to detect the expression of TSLP in nasal polyps tissues and ELISA method to the expression of IL-4, IL-5, IFN-gamma, IL-13 and analyzed the correlation between them. RESULT: The expression of TSLP in nasal polyp tissues was higher than that in normal inferior turbinate mucosa (P < 0.05). The expression level of IL-4, IL-5, IFN-gamma and IL-13 in nasal polyps tissues were significantly higher than those in control group (P < 0.05). TSLP staining was a statistically significant positive correlation with IL-4, IL5 and IL-13 (r = 0.475, 0.594 and 0.582, respectively, P < 0.01), while inverse correlation with IFN-gamma (r = -0.614, P < 0.01). CONCLUSION The high expression of TSLP might promote T cell differentiation towards Th2, and participated in the occurrence/development of nasal polyps, aggravated the nose Th2 inflammatory response.
Adult ; Cytokines ; metabolism ; Female ; Humans ; Interferon-gamma ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-5 ; metabolism ; Male ; Nasal Polyps ; immunology ; metabolism ; Th2 Cells ; immunology ; Young Adult

OBJECTIVETo evaluate the effect of intranasal liposome-mediated IL-12 gene therapy on the eosinophils and IL-5 in the murine model of allergic rhinitis.

METHODSThirty-six BALB/C mice were randomly divided into allergic rhinitis (AR) group, gene therapy group and control group. Allergic rhinitis group were sensitized and stimulated by ovalbumin (OVA), and gene therapy group were administered with liposome-mediated pGEG. mIL-12 transnasally before stimulated. The eosinophils in bone marrow were counted by Wright's staining, and the eosinophils in nasal mucosa were counted by HE staining. The eosinophils of peripheral blood were detected by flow cytometry. The expression of IL-5 in bone marrow and nasal mucosa was examined by immunohistochemistry. The IL-5 in serum was detected by ELISA.

RESULTSAmong the three groups, the difference of all data was statistically significant (P<0.01). Multiple Comparison showed that the ratio of eosinophils to white cells and the mount of IL-5 positive cells in nasal mucosa and bone marrow of gene therapy group was significantly lower than that of AR group (P<0.05). The ratio of eosinophils to granulocyte (0.124 +/- 0.031) and the expression level of IL-5 [(29.51 +/- 6.68) pg/ml] in peripheral blood [ 0.184 +/- 0.079 and (56.58 +/- 16.80) pg/ml] were significantly lower in gene therapy group than in AR group (P<0.05).

CONCLUSIONSTransnasal administration of liposome- mediated pGEG. mIL-12 could depress the expression of IL-5 in bone marrow, peripheral blood, and nasal mucosa, to influence the proliferation and differentiation of eosinophils and decrease the delivery and transference of eosinophils to peripheral blood and nasal mucosa. It may be a new treatment for respiratory tract allergic inflammation.

Animals ; Eosinophils ; metabolism ; Genetic Therapy ; Interleukin-12 ; genetics ; pharmacology ; Interleukin-5 ; metabolism ; Liposomes ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa ; metabolism ; Rhinitis, Allergic, Perennial ; metabolism ; therapy

OBJECTIVETo investigate the correlation between nuclear factor-kappa B (NF-kappaB) activity and cytokine expression in nasal mucosa of chronic sinusitis.

METHODSIL-5, IL-6 and IL-8 levels in nasal mucosa were assayed by the method of ELISA in 52 cases of chronic sinusitis [concomitant with allergic rhinitis (AR group), without allergic rhinitis (NAR group)] and 12 normal subjects. Semi-quantitative RT-PCR and immunohistochemical staining were used to examine P50 and P65 subunits of NF-KB expressions and activation in nasal mucosa. The correlation between activities of NF-KB P50 and P65 subunits and cytokine expression was evaluated.

RESULTSIL-5, IL-6 and IL-8 levels in both AR and NAR groups were significantly increased (all P < 0.01 for AR group; P < 0.05, 0.05, 0.01, respectively, for NAR group, as compared with normal group), and the levels were much higher in AR group than that in NAR group (P < 0.01, 0.05, 0.01, respectively). The levels of P50 and P65 mRNA in both AR and NAR groups were enhanced (all P < 0.01 for AR group; all P < 0.01 for NAR group, as compared with normal group), and AR group had markedly greater P50 and P65 mRNA levels in comparison with NAR group (both P < 0.05). Immunohistochemical study revealed that nucleus-present rates of P50 and P65 in both AR and NAR groups were significantly higher than those of control group (all P < 0.01), and they were much greater in AR group as compared with NAR group (all P < 0.01). Pearson correlation analysis demonstrated that P50 and P65 nucleus-present rates were closely correlated with IL-6 and IL-8 levels, but not IL-5. The correlation coefficient was 0. 49 for P50 and IL-6, 0. 54 for P50 and IL-8, 0. 61 for P65 and IL-6, and 0.66 for P65 and IL-8 (all P < 0.01).

CONCLUSIONSActivation of P50 and P65 subunits of NF-kappaB might be one of the mechanisms for induction of IL-6 and IL-8 expression in chronic sinusitis. Concomitance of allergic rhinitis with chronic sinusitis further increased activities of NF-kappaB subunits, and further elevated IL-6 and IL-8 expression. IL-5 expression was independent of NF-kappaB pathway in chronic sinusitis.

Adult ; Chronic Disease ; Female ; Humans ; Interleukin-5 ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Male ; Middle Aged ; NF-kappa B p50 Subunit ; metabolism ; Nasal Mucosa ; metabolism ; RNA, Messenger ; genetics ; Rhinitis ; metabolism ; Sinusitis ; metabolism ; Transcription Factor RelA ; metabolism

OBJECTIVE: To explore the prophylactic effect of Budesonide on the expression of IL-4,IL-5 in nasal mucosa in model of minimal persistent inflammation of allergic rhinitis in rats. METHOD: Eighty SD rats were randomly divided into allergic rhinitis group (A group), experimental (B group), control group (C group) and negative control group (D group). A group was made for model of allergic rhinitis. B and C group were made for model of the lightest persistent inflammatory response. After the models were established, half of rats in the A group, B group, C group and D group were executed, and EOS infiltration and the expression of IL-4, IL-5, ICAM-1 were observed in nasal mucosa. The remaining rats of B group were given budesonide (64 microg/side/time, twice/day) treatment for 2 weeks. A, C, D group were given nasal spray with normal saline for 2 weeks. After that A, B, and C groups were stimulated with 1% OVA daily for one week, D group were given nasal spray with normal saline. All rats were executed after excitation, EOS infiltration and IL-4, IL-5 expression were observed. RESULT: After the drug treatment, B group only had a small amount of mucous EOS infiltration and had no significant difference with D group, but in A and C group EOS had heavy infiltration. Gray value of the IL-4 positive areas in B group were significantly different compared with A and C group (P < 0.05), A group and C group had no significant difference (P > 0.05). Distribution of IL-5 positive signals was similar with that of IL-4. CONCLUSION Budesonide MPI application could significantly inhibit the allergic.
Animals ; Budesonide ; therapeutic use ; Disease Models, Animal ; Female ; Interleukin-4 ; metabolism ; Interleukin-5 ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic ; metabolism ; prevention & control

OBJECTIVETo explore the correlation between the expression of GATA-3 and the level of local cytokines (IL-5, IL-6 and IL-8).

METHODSThe levels of IL-5, IL-6 and IL-8 in ethmoid sinus mucosa were titrated in 45 patients with chronic rhinosinusitis and 11 normal subjects by ELISA. Patients were divided into AR group (with allergic rhinitis) and NAR group (without allergic rhinitis) . Semi-quantitative RT-PCR and immunohistochemical staining were used to examine the GATA-3 expression in nasal mucosa. The correlation between the expression of GATA-3 and the levels of cytokines was evaluated.

RESULTSIL-5, IL-6 and IL-8 levels in both AR and NAR groups were significantly elevated compared with normal group (all P < 0.01 for AR group; P < 0.05, 0.05, 0.01 for NAR group, respectively), and they were much higher in AR group in comparison with NAR group (P < 0.01, 0.05, 0.01, respectively). Semi-quantitative RT-PCR showed that AR and NAR groups had markedly greater level of GATA-3 mRNA than that in control group (P < 0.01, respectively), and the level of GATA-3 mRNA in AR group was further higher than that in NAR group (P < 0.01). Immunohistochemical staining illustrated that GATA-3 was primarily presented in cytoplasma and the GATA-3 positive cells were mainly infiltrating inflammatory cells in submucosa. The mean GATA-3 positive-staining rate was (27. 90 +/- 16.75)% and (10.22 +/- 0.05)% in AR and NAR group, which were markedly higher than (1.30 +/- 1.78)% in control group (P < 0.01, respectively). Pearson correlation analysis demonstrated that GATA-3 positive-staining rate was closely correlated with IL-5 level, but not IL-6 and IL-8. The correlation coefficient was 0. 712 for GATA-3 and IL-5 (P < 0.01), 0.200 for GATA-3 and IL-6 (P > 0.05), 0.089 for GATA-3 and IL-8 (P > 0.05).

CONCLUSIONSActivation of GATA-3 might be one of the mechanisms for induction of IL-5 expression in chronic rhinosinusitis . Concomitance of allergic rhinitis with chronic rhinosinusitis further increased expression of GATA-3, and subsequently enhanced IL-5 expression. Chronic sinusitis may be related to allergy, and GATA-3 may play a key role in the pathogenesis of chronic sinusitis.

Adolescent ; Adult ; Aged ; Chronic Disease ; Female ; GATA3 Transcription Factor ; metabolism ; Humans ; Interleukin-5 ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Male ; Middle Aged ; Nasal Mucosa ; metabolism ; Sinusitis ; metabolism ; Young Adult

BACKGROUNDExpression of murine calcium-activated chloride channel family member 3 (mCLCA3) has been reported to be increased in the airway epithelium of asthmatic mice challenged with ovalbumin (OVA). However, its role in asthmatic airway inflammation under no OVA exposure has not yet been clarified.

METHODSmCLCA3 plasmids were transfected into the airways of normal BALB/c mice. mCLCA3 expression and airway inflammation in mouse lung tissue were evaluated. Cell differentials and cytokines in bronchoalveolar lavage fluid (BALF) were analyzed. The expression of mCLCA3 protein and mucus protein mucin-5 subtype AC (MUC5AC) were analyzed by Western blotting. The mRNA levels of mCLCA3, MUC5AC and interleukin-13 (IL-13) were determined quantitatively.

RESULTSmCLCA3 expression was not detected in the control group while strong immunoreactivity was detected in the OVA and mCLCA3 plasmid groups, and was strictly localized to the airway epithelium. The numbers of inflammatory cells in lung tissue and BALF were increased in both mCLCA3 plasmid and OVA groups. The protein and mRNA levels of mCLCA3 and MUC5AC in the lung tissue were significantly increased in the mCLCA3 plasmid and OVA groups compared to the control group. The level of IL-13, but not IL-4, IL-5, IFN-γ, CCL2, CCL5 or CCL11, was significantly increased compared with control group in BALF in the mCLCA3 plasmid and OVA groups. The level of IL-13 in the BALF in the mCLCA3 plasmid group was much higher than that in the OVA group (P < 0.05). The level of mCLCA3 mRNA in lung tissue was positively correlated with the levels of MUC5AC mRNA in lung tissue, IL-13 mRNA in lung tissue, the number of eosinophils in BALF, and the content of IL-13 protein in BALF. The level of IL-13 mRNA in lung tissue was positively correlated with the number of eosinophils in BALF and the level of MUC5AC mRNA in lung tissue.

CONCLUSIONThese findings suggest that increased expression of a single-gene, mCLCA3, could simulate an asthma attack, and its mechanism may involve mCLCA3 overexpression up-regulating IL-13 expression.

Allergens ; Animals ; Asthma ; Chloride Channels ; Female ; Inflammation ; chemically induced ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-4 ; genetics ; metabolism ; Interleukin-5 ; genetics ; metabolism ; Mice ; Mice, Inbred BALB C ; Mucin 5AC ; genetics ; metabolism ; Ovalbumin ; pharmacology

OBJECTIVETo explore the effect of different doses of 1,25-(OH)(2)VitD(3) early supplementation on airway inflammation and lung inflammatory factors in baby rats with asthma.

METHODSForty male weaned Wistar rats were divided into normal group, model group, low 1,25-(OH)(2)VitD(3) group, middle 1,25-(OH)(2)VitD(3) group, high 1,25-(OH)(2)VitD(3) group using random number table (8 rats each group). The rats in low, middle and high 1,25-(OH)(2)VitD(3) groups were given 1, 4, 10 µg/kg of 1,25-(OH)(2)VitD(3) every other day by intraperitoneal injection respectively for 25 days. Except normal group, the rats in other groups were challenged with ovalbumin to establish the asthma model. The pathologic changes of lung tissue, the total white blood cell and classified cell counts in bronchoalveolar lavage fluid (BALF) were measured. The concentrations of IL-4, IL-5 and IFN-γ in serum and BALF were measured by ELISA method.

RESULTSThe level of total white blood cell counts in BALF were (5.98 ± 1.67)×10(5)/ml, (25.34 ± 4.28)×10(5)/ml, (17.24 ± 3.3)×10(5)/ml, (9.31 ± 3.37)×10(5)/ml, (45.1 ± 15.75)×10(5)/ml, respectively (F = 33.453, P < 0.01). The percent ratio of EOS in BALF were (1.44 ± 0.78)%, (17.81 ± 6.88)%, (15.00 ± 5.70)%, (8.89 ± 3.66)%, (25.88 ± 5.57)%, respectively (F = 27.299, P < 0.01). The level of IL-4 in serum of normal, model, low, middle and high-1,25-(OH)(2)VitD(3) groups were (0.62 ± 0.54), (7.57 ± 1.04), (3.58 ± 0.56), (2.70 ± 0.78) and (5.27 ± 0.30) pg/ml, respectively (F = 116.287, P < 0.01); IL-5 in resume were (32.20 ± 4.23), (67.14 ± 18.14), (37.51 ± 0.47), (40.69 ± 2.47) and (124.60 ± 36.19) pg/ml, respectively (F = 23.902, P < 0.01); IFN-γ in serum were (79.71 ± 10.08), (49.06 ± 4.46), (59.15 ± 2.51), (59.27 ± 2.33) and (53.85 ± 1.97) pg/ml, respectively (F = 39.954, P < 0.01). Also in BLAF, the IL-4 of all groups were (0.51 ± 0.30), (102.92 ± 54.61), (8.64 ± 4.07), (3.10 ± 1.28) and (33.67 ± 8.1) pg/ml, respectively (F = 24.062, P < 0.01); the IFN-γ were (247.37 ± 189.18), (43.82 ± 13.76), (81.32 ± 17.07), (86.50 ± 14.26) and (59.89 ± 34.17) pg/ml, respectively (F = 7.157, P < 0.01); the IL-5 in BALF were (38.81 ± 0.60), (80.48 ± 17.90), (45.11 ± 1.33), (43.39 ± 1.11) and (149.60 ± 45.87) pg/ml, respectively (F = 35.978, P < 0.01). Pathologic changes in lung of asthma rat groups were obvious. The lung pathologic changes in low and middle dose groups showed a significant improvement compared to the asthma group and high dosage group showed more serious pathologic changes compared to the low and middle dose groups.

CONCLUSIONIntervention with appropriate dose of 1,25-(OH)(2)VitD(3) in the early life could improve lung pathologic changes and reduce the effect of inflammatory factors in air way of baby rat asthma model. However, overdose might play detrimental effect.

Animals ; Asthma ; metabolism ; pathology ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-5 ; metabolism ; Lung ; metabolism ; pathology ; Male ; Pneumonia ; metabolism ; pathology ; Rats ; Rats, Wistar ; Vitamin D ; administration & dosage ; pharmacology

OBJECTIVETo evaluate the effects of Staphylococcus aureus enterotoxin B (SEB) on proinflammatory cytokine/chemokine releases in primary human nasal epithelial cell (HNEC).

METHODSEpithelial cells of nasal polyps (NP) and inferior turbinate (IT) were cultured without serum under stimulus of SEB 1, 10, 100 ng/ml, IL-1beta 20 ng/ml and SEB 10 ng/ml + dexamethasone 13 ng/ml for 12,24 and 48 h, respectively. The expression of IL-5 and Granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA derived from epithelial cells was detected by in situ hybridization.

RESULTS(1) The expression of IL-5 and GM-CSF mRNA was time and dose-dependent, and reached to a peak under SEB 10 ng/ml for 24 h (P < 0.05). The mRNA expressed more intensively in epithelial cells from NP than IT (P < 0.05). (2) The expression of IL-5 and GM-CSF mRNA increased less under the stimulus of IL-1beta than SEB 10 ng/ml (P < 0.05). (3) The mRNA level of IL-5 and GM-CSF decreased under the stimulus of SEB + dexamethasone 13 ng/m when compared with the stimulus of SEB 10 ng/ml (P < 0.05).

CONCLUSIONSEB showed proinflammatory effects on HNEC.

Cells, Cultured ; Dexamethasone ; pharmacology ; Enterotoxins ; pharmacology ; Epithelial Cells ; metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor ; metabolism ; Humans ; Interleukin-1beta ; metabolism ; Interleukin-5 ; metabolism ; Nasal Mucosa ; cytology ; metabolism ; pathology ; RNA, Messenger ; metabolism