Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-gamma has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-gamma were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Ralpha1/alpha2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-gamma levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Ralpha1, rather than IL-13Ralpha2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease.
Adult ; Female ; Humans ; Idiopathic Interstitial Pneumonias/diagnosis/*metabolism ; Idiopathic Pulmonary Fibrosis/diagnosis/*metabolism ; Interferon-gamma/analysis ; Interleukin-13/*analysis ; Interleukin-13 Receptor alpha1 Subunit/*metabolism ; Interleukin-13 Receptor alpha2 Subunit/*metabolism ; Interleukin-4/analysis ; Lung/physiopathology ; Male ; Middle Aged

OBJECTIVETo study the effects of the change in transient receptor potential vanilloid 1 (TRPV1) channel activity on the degree of airway inflammation in asthmatic mice.

METHODSBALB/c mice were randomly divided into control, asthma, capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist), and dexamethasone groups. The asthmatic mouse model was established by intraperitoneal injection of mixed ovalbumin-aluminium hydroxide solution and ultrasonic atomization with OVA for sensitization and challenge. The capsaicin, capsazepine, and dexamethasone groups were given intraperitoneal injection of capsaicin (30 μg/kg), capsazepine (10 μmol/kg), and dexamethasone (2 mg/kg) respectively, at 30 minutes before challenge. Hematoxylin and eosin staining was used to observe the degree of pulmonary inflammation. ELISA was used to measure the content of interleukin-8 (IL-8) and interleukin-13 (IL-13) in bronchoalveolar lavage fluid (BALF). Real-Time PCR was used to measure the relative content of TRPV1 mRNA in lung tissue.

RESULTSCompared with the asthma group, the capsazepine and dexamethasone groups showed reduced pulmonary inflammation, while the capsaicin group showed aggravated pulmonary inflammation. Compared with the control group, the asthma and capsaicin groups showed increases in the content of IL-13 and IL-8 in BALF and the mRNA expression of TRPV1 in lung tissue (P<0.05). Compared with the asthma group, the capsazepine and dexamethasone groups showed reductions in the content of IL-13 and IL-8 in BALF and the mRNA expression of TRPV1 in lung tissue (P<0.05). The capsaicin group showed increases in the content of IL-13 and IL-8 in BALF (P<0.05).

CONCLUSIONSTRPV1 channel agonist and antagonist can influence the degree of airway inflammation in asthmatic mice. Dexamethasone may reduce airway inflammation through regulating TRPV1 level.

Animals ; Asthma ; etiology ; Female ; Interleukin-13 ; analysis ; Interleukin-8 ; analysis ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; RNA, Messenger ; analysis ; TRPV Cation Channels ; genetics ; physiology

OBJECTIVETo study the concentrations of IL-4 and IL-13 in bronchoalveolar lavage fluid (BALF) in neonates with respiratory distress syndrome (RDS) and concurrent ventilator-associated pneumonia (VAP).

METHODSSixty-eight neonates with RDS undergoing mechanical ventilation for over 48 hrs were enrolled. IL-4 and IL-13 levels in BALF were measured using ELISA 1, 72 and 96 hrs after mechanical ventilation. The results were compared between the neonates with concurrent VAP (n=37) and without (n=31).

RESULTSThe levels of BALF IL-4 96 hrs after ventilation in the VAP group (35.34+/-1.78 ng/mL) were significantly higher than those in the non-VAP group (13.69+/-2.47 ng/mL, P<0.05). The levels of BALF IL-13 96 hrs after ventilation in the VAP group (33.74+/-2.74 ng/mL) also increased significantly compared with those in the non-VAP group (13.50+/-3.81 ng/mL) (P<0.05). There were significant differences in BALF IL-4 and IL-13 levels between 1 hr and 96 hrs in the VAP group (P<0.05).

CONCLUSIONSBALF IL-4 and IL-13 levels increase in neonates with RDS and concurrent VAP. IL-4 and IL-13 may involve in the regulation of the inflammatory immune response.

Bronchoalveolar Lavage Fluid ; immunology ; Female ; Humans ; Infant, Newborn ; Interleukin-13 ; analysis ; Interleukin-4 ; analysis ; Male ; Microbial Sensitivity Tests ; Pneumonia, Ventilator-Associated ; immunology ; microbiology ; Respiratory Distress Syndrome, Adult ; immunology

The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1beta, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1beta in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1beta and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders.
Acari/drug effects/physiology ; Adolescent ; Adult ; Aged ; Animals ; Blepharitis/drug therapy/*immunology/parasitology ; Chemokine CCL4/analysis ; Female ; Granulocyte Colony-Stimulating Factor/analysis ; Humans ; Interleukin-12/analysis ; Interleukin-13/analysis ; Interleukin-17/analysis ; Interleukin-1beta/analysis ; Interleukin-5/analysis ; Interleukin-7/analysis ; Male ; Middle Aged ; Tea Tree Oil/therapeutic use ; Tears/metabolism

PURPOSE: The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application. METHODS: A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators. RESULTS: The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses. CONCLUSIONS: The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.
Asian Continental Ancestry Group ; Chemokines ; Classification ; Collagen Type I ; Cytokines ; Eosinophils ; Humans ; Immunoassay ; Interleukin-10 ; Interleukin-13 ; Interleukin-17 ; Interleukin-23 Subunit p19 ; Nasal Polyps ; Passive Cutaneous Anaphylaxis ; Principal Component Analysis ; Prognosis ; Rhinitis ; RNA, Messenger ; Sinusitis ; Transcription Factors ; Up-Regulation

OBJECTIVEPPAR-gamma is associated with the differentiation, apoptosis, proliferation and cytokine secretion of immunologic cells. This study investigated peripheral blood lymphoblastic PPAR-gamma mRNA expression and its correlation with plasma IL-13 contents in children with acute idiopathic thrombocytopenic purpura (ITP).

METHODSFifty-three children with acute ITP who were in line with the standard test between September 2007 and July 2008 were enrolled. Fifty healthy children during the same period were used as the control group. PPAR-gamma mRNA expression in peripheral blood lymphocytes were detected by RT-PCR. Plasma IL-13 contents were detected using ELISA.

RESULTSPPAR-gamma mRNA expression in peripheral blood lymphocytes from acute ITP children were significantly higher than that in the control group (0.78 +/- 0.03 vs 0.52 +/- 0.05; P< 0.05). Plasma IL-13 contents in children with acute ITP were also significantly higher than those in the control group (160.21 +/- 34.26 pg/mL vs 121.42 +/- 12.69 pg/mL; P< 0.05). There was a positive correlation between plasma IL-13 level and lymphoblastic PPAR-gamma mRNA expression in children with ITP (r=0.89, P< 0.05).

CONCLUSIONSPPAR-gamma mRNA expression in peripheral blood lymphocytes increased and were positively correlated with plasma IL-13 contents in children with acute ITP, suggesting that PPAR-gamma and IL-13 might participate in the pathogenesis of acute ITP.

Acute Disease ; Child ; Child, Preschool ; Female ; Humans ; Interleukin-13 ; blood ; physiology ; Lymphocytes ; metabolism ; Male ; PPAR gamma ; genetics ; physiology ; Purpura, Thrombocytopenic, Idiopathic ; etiology ; immunology ; RNA, Messenger ; analysis

OBJECTIVETo investigate the changes in plasma level of interleukin-13 (IL-13) and the changes in the pulmonary IL-13 mRNA content and the pulmonary activator protein-1 (AP-1) activity of the rats inflicted with acute lung injury (ALI) induced by lipopolysaccharide (LPS), so as to explore the relationship between IL-13 expression and AP-1 activity.

METHODSOne hundred and twenty Wistar rats were employed in the study and were randomly divided into A (2 mg/kg), B (4 mg/kg), C (6 mg/kg) and D (8 mg/kg) groups according to different dosage of LPS administration and a control group (NS group) at each observing time point. The rats were observed at 1, 2, 4 and 6 postburn hours (PBHs) and every 6 rats were deployed in every group and each time points. A model of systemic inflammatory response syndrome-acute lung injury (SIRS-ALI) was replicated in Wistar rats. The plasma content of IL-13 was assayed by enzyme-linked immunosorbent assay (ELISA), and the pulmonary tissue content of IL-13 mRNA and AP-1 activity by reverse transcriptase-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assays (EMSA).

RESULTSThe plasma content of IL-13, pulmonary content of IL-13 mRNA and AP-1 activity increased simultaneously after LPS administration. All the above indices were significantly different statistically between the LPS groups and the control group (P < 0.05 - 0.01). The plasma level of IL-13 and pulmonary tissue mRNA content and AP-1 activity in A, B, C and D groups were increased significantly with peak levels at 2 PBHs.

CONCLUSIONThe pulmonary AP-1 activity increased with the enhanced expression of IL-13, which was related to the development of SIRS-ALI.

Acute Lung Injury ; metabolism ; Animals ; Endotoxins ; toxicity ; Female ; Interleukin-13 ; blood ; genetics ; physiology ; Lung ; chemistry ; Male ; Rats ; Rats, Wistar ; Transcription Factor AP-1 ; analysis ; physiology

OBJECTIVETo study serum concentration and mRNA expression of interleukin-13 (IL-13) in children with steroid-responsive nephrotic syndrome (SRNS) and the effect of methylprednisolone pulse therapy (MPT) on IL-13 expression.

METHODSTwenty-eight children with SRNS were enrolled in this study. Serum protein level of IL-13 was measured using ELISA and IL-13 mRNA expression in peripheral blood mononuclear cells (PBMC) was detected with RT-PCR before MPT, 2 and 5 days after MPT, and 2 weeks after disappearance of proteinuria following MPT. Twenty-four urinary protein was measured with the biuret assay. Twenty healthy children were used as controls.

RESULTSSerum IL-13 levels (38.48 +/- 13.01 pg/mL vs 5.18 +/- 2.71 pg/mL) and PBMC IL-13 mRNA expression (1.31 +/- 0.23 vs 0.36 +/- 0.07) before MPT in SRNS patients were significantly higher than in the controls. After 5 days of MPT and 2 weeks after disappearance of proteinuria following MPT, serum IL-13 levels (15.33 +/- 7.81 and 5.35 +/- 2.12 pg/mL respectively) and PBMC IL-13 mRNA expression (0.89 +/- 0.26 and 0.33 +/- 0.08 respectively) were significantly reduced (P < 0.01). Serum IL-13 levels and PBMC IL-13 mRNA expression in SRNS patients 2 weeks after disappearance of proteinuria following MPT were reduced to control levels, but remained at a higher level than controls 5 days after MPT. A positive correlation was found between serum levels of IL-13 and 24-hour urinary protein in SRNS patients before (r=0.75, P < 0.01) and after 2 and 5 days of MPT (r=0.68, r=0.71 respectively; P < 0.05).

CONCLUSIONSSerum IL-13 levels and PBMC IL-13 mRNA expression in children with SRNS increase. MPT can inhibit the expression of protein and mRNA of IL-13 in these patients.

Adolescent ; Child ; Female ; Humans ; Interleukin-13 ; blood ; genetics ; Male ; Methylprednisolone ; administration & dosage ; Nephrotic Syndrome ; blood ; drug therapy ; Proteinuria ; drug therapy ; RNA, Messenger ; analysis

Nutrigenomics refers to research that investigates the interaction between nutrition and the human genome. Caffeine in tea and coffee is widely and routinely consumed by people. This study was performed to confirm the effect of caffeine treatment on the gene expression and cytokine profiling in 3T3-L1 adipocyte cells using microarray and protein array methodology. Treatment of caffeine in 3T3-L1 adipocyte cells increased expression of several genes related with obesity including adipocyte C1Q and collagen domain containing (ACDC), Adipsin (ADN), uncoupling protein 3 (UCP3), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is known as lipid storage enzyme, was decreased by caffeine treatment. Furthermore, cytokines, such as interleukin-3 (IL-3), interleukin-12 (IL-12), interleukin-13 (IL-13), granulocyte colony stimulating factor (GCSF), granulocyte macrophage colony stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF), were decreased in caffeine treated 3T3-L1 adipocyte cells. These results provided interesting information about the genes related with caffeine and cytokine expression profiling in obesity.
Adipocytes* ; Caffeine* ; Coffee ; Collagen ; Colony-Stimulating Factors ; Complement Factor D ; Cytokines ; Gene Expression ; Genome, Human ; Granulocyte-Macrophage Colony-Stimulating Factor ; Granulocytes ; Humans ; Interleukin-12 ; Interleukin-13 ; Interleukin-3 ; Nutrigenomics ; Obesity ; Oxidoreductases ; Protein Array Analysis ; Tea ; Vascular Endothelial Growth Factor A

PURPOSE: Different characteristics of airway microbiome in asthmatics may lead to differential immune responses, which in turn cause eosinophilic or neutrophilic airway inflammation. However, the relationships among these factors have yet to be fully elucidated.METHODS: Microbes in induced sputum samples were subjected to sequence analysis of 16S rRNA. Airway inflammatory phenotypes were defined as neutrophils (>60%) and eosinophils (>3%), and inflammation endotypes were defined by levels of T helper (Th) 1 (interferon-γ), Th2 (interleukin [IL]-5 and IL-13), Th-17 (IL-17), and innate Th2 (IL-25, IL-33, and thymic stromal lymphopoietin) cytokines, inflammasomes (IL-1β), epithelial activation markers (granulocyte-macrophage colony-stimulating factor and IL-8), and Inflammation (IL-6 and tumor necrosis factor-α) cytokines in sputum supernatants was assessed by enzyme-linked immunosorbent assay.RESULTS: The numbers of operational taxonomic units were significantly higher in the mixed (n = 21) and neutrophilic (n = 23) inflammation groups than in the paucigranulocytic inflammation group (n = 19; p < 0.05). At the species level, Granulicatella adiacens, Streptococcus parasanguinis, Streptococcus pneumoniae, Veillonella rogosae, Haemophilus parainfluenzae, and Neisseria perflava levels were significantly higher in the eosinophilic inflammation group (n = 20), whereas JYGU_s levels were significantly higher in the neutrophilic inflammation group compared to the other subtypes (P < 0.05). Additionally, IL-5 and IL-13 concentrations were correlated with the percentage of eosinophils (P < 0.05) and IL-13 levels were positively correlated with the read counts of Porphyromonas pasteri and V. rogosae (P < 0.05). IL-1β concentrations were correlated with the percentage of neutrophils (P < 0.05). had a tendency to be positively correlated with the read count of JYGU_s (P = 0.095), and was negatively correlated with that of S. pneumoniae (P < 0.05).CONCLUSIONS: Difference of microbial patterns in airways may induce distinctive endotypes of asthma, which is responsible for the neutrophilic or eosinophilic inflammation in asthma.
Asthma ; Colony-Stimulating Factors ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Haemophilus parainfluenzae ; Inflammasomes ; Inflammation ; Interleukin-13 ; Interleukin-33 ; Interleukin-5 ; Microbiota ; Necrosis ; Neisseria ; Neutrophils ; Phenotype ; Pneumonia ; Porphyromonas ; Sequence Analysis ; Sputum ; Streptococcus ; Streptococcus pneumoniae ; Veillonella