OBJECTIVETo study the value of eosinophils (EOS) and interleukin-17 (IL-17) in nasopharyngeal secretions in the evaluation of progress of wheezing in children under 5 years old.

METHODSFifty-three children under five years old who had recurrent wheezing were classified into two groups: wheezing group I with atopic body (n=27) and wheezing group II without atopic body (n=26). Twenty pre-surgical children with non-infectious disease were used as the control group. Nasopharyngeal secretions were collected. Inflammatory cells in nasopharyngeal secretions were counted under the microscope. IL-17 levels in supernatants were measured using ELISA.

RESULTSEOS counts in nasopharyngeal secretions in wheezing group I were significantly higher than those in wheezing group II and the control group (p<0.05, p<0.01, respectively). There were no significant differences in EOS counts between wheezing II and the control groups. The IL-17 levels in both wheezing groups were significantly higher than those in the control group (p<0.01), and the wheezing group I had increased IL-17 levels than wheezing group II (1 474+/-974 pg/mL vs 788+/-132 pg/mL; p<0.05). The IL-17 level was positively correlated with the EOS counts in wheezing group I (r=0.62, p<0.05).

CONCLUSIONSEOS counts and IL-17 levels in nasopharyngeal secretions may be used as indices for identifying the tendency to develop asthma in children under 5 years old with wheezing.

Child, Preschool ; Eosinophils ; physiology ; Female ; Humans ; Infant ; Interleukin-17 ; analysis ; Leukocyte Count ; Male ; Nasopharynx ; secretion ; Respiratory Sounds ; 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: Chronic rhinosinusitis (CRS) is a complex immunological condition, and novel experimental modalities are required to explore various clinical and pathophysiological endotypes; mere evaluation of nasal polyp (NP) status is inadequate. Therefore, we collected patient nasal secretions on filter paper and characterized the proteomes. METHODS: We performed liquid chromatography-mass spectrometry (MS)/MS in the data-dependent acquisition (DDA) and data-independent acquisition (DIA) modes. Nasal secretions were collected from 10 controls, 10 CRS without NPs (CRSsNP) and 10 CRS with NPs (CRSwNP). We performed Orbitrap MS-based proteomic analysis in the DDA (5 controls, 5 CRSsNP and 5 CRSwNP) and the DIA (5 controls, 5 CRSsNP and 5 CRSwNP) modes, followed by a statistical analysis and a hierarchical clustering to identify differentially expressed proteins in the 3 groups. RESULTS: We identified 2,020 proteins in nasal secretions. Canonical pathway analysis and gene ontology (GO) evaluation revealed that interleukin (IL)-7, IL-9, IL-17A and IL-22 signaling and neutrophil-mediated immune responses like neutrophil degranulation and activation were significantly increased in CRSwNP compared to control. The GO terms related to the iron ion metabolism that may be associated with CRS and NP development. CONCLUSIONS: Collection of nasal secretions on the filter paper is a practical and non-invasive method for in-depth study of nasal proteomics. Our proteomic signatures also support that Asian NPs could be characterized as non-eosinophilic inflammation features. Therefore, the proteomic profiling of nasal secretions from CRS patients may enhance our understanding of CRS endotypes.
Asian Continental Ancestry Group ; Gene Ontology ; Humans ; Inflammation ; Interleukin-17 ; Interleukin-9 ; Interleukins ; Iron ; Metabolism ; Methods ; Nasal Polyps ; Neutrophils ; Proteome ; Proteomics ; Sinusitis ; Spectrum Analysis

Adult ; Asthma ; drug therapy ; immunology ; Budesonide ; therapeutic use ; Cell Differentiation ; Eosinophil Cationic Protein ; analysis ; Female ; Humans ; Interleukin-17 ; analysis ; Interleukin-8 ; analysis ; Male ; Middle Aged ; Neutrophils ; physiology ; Peroxidase ; analysis ; Prospective Studies ; Sputum ; cytology ; immunology

OBJECTIVETo investigate the changes in the levels of interleukin-17 (IL-17) and transforming growth factor beta 1 (TGF-β1) in serum and bronchoalveolar lavage fluid (BALF) and their clinical significance among children with asthma.

METHODSFifty-six children with asthma were divided into moderate or severe asthma (n=37) and mild asthma groups (n=19) and 18 children without asthma were selected as the control group. Cells in BALF were counted under a microscope. The levels of IL-17 and TGF-β1 in serum and BALF were measured using ELISA.

RESULTSwere no significant differences in total cell count and percentage of macrophages between the two asthma groups and the control group (P>0.05). The percentages of neutrophils, eosinophils and epithelial cells in BALF were significantly higher in the two asthma groups than in the control group (P<0.05). The two asthma groups had significantly higher levels of IL-17 and TGF-β1 in serum and BALF than the control group (P<0.05), and the moderate or severe asthma group had significantly higher levels of IL-17 and TGF-β1 in serum and BALF than the mild asthma group (P<0.05). Levels of IL-17 and TGF-β1 in serum were significantly positively correlated with those in BALF (r=0.935 and 0.943, P<0.05 for both). In children with asthma, serum IL-17 level was significantly positively correlated with the percentage of neutrophils, eosinophils and epithelial cells in BALF (r=0.802, 0.799, and 0.674, P<0.05 for all), and a significant positive correlation was also seen between serum levels of IL-17 and TGF-β1 (r=0.878, P<0.05).

CONCLUSIONSLevels of IL-17 and TGF-β1 in serum and BALF are elevated in children with asthma. IL-17 and TGF-β1 may be involved in the occurrence and development of asthma, and they play important roles in asthma attack and aggravation.

Asthma ; immunology ; pathology ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Interleukin-17 ; analysis ; blood ; physiology ; Male ; Transforming Growth Factor beta1 ; analysis ; blood ; physiology

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

PURPOSE: Endotype in chronic rhinosinusitis (CRS) has been established in the last decade. However, the exact immunologic profile of CRS still has controversy because it has a considerable immunologic heterogeneity. Therefore, we investigated various inflammatory mediators according to different nasal tissues in chronic rhinosinusitis and compared them within the same subject. METHODS: We collected uncinate process mucosa (UP) and nasal polyp (NP) tissues from controls, CRS without NP (CRSsNP) and CRS with NP (CRSwNP). Expression levels of 28 inflammatory mediators including T helper (Th) 1, Th2, Th17, proinflammatory cytokines and remodeling markers were determined by multiplex immunoassay and were analyzed using paired tests as well as principal component analysis (PCA) to investigate endotype in each subtype of CRS. RESULTS: Signature inflammatory mediators are interleukin (IL)-5, C-C motif chemokine ligand (CCL)-24, monocyte chemoattractant protein (MCP)-4, and vascular cell adhesion molecule (VCAM)-1 in eosinophilic NP, whereas IL-17A, IL-1β, and matrix metallopeptidase (MMP)-9 were detected as signature inflammatory markers in non-eosinophilic NP. Despite differences in inflammatory cytokine profile between eosinophilic and non-eosinophilic NP, the common upregulation of IL-5, CCL-11, IL-23, IL-2Rα, VCAM-1, MMP-3 and MMP-9 were shown in NP compared to UP within the same subject. In the PCA, we observed that Th2 immune response was helpful in discriminating between nasal tissues in subtypes of CRS and that there was a partial overlap between non-eosinophilic NP and eosinophilic NP in terms of Th2 mediators. CONCLUSIONS: Commonly upregulated mediators in NP were Th2-associated, compared with UP regardless of CRS subtypes, whereas signature markers were distinct in each NP subtype. These findings imply that Th2 inflammatory responses may play a role in the development of NP regardless of CRSwNP subtypes.
Cytokines ; Eosinophils ; Immunoassay ; Interleukin-17 ; Interleukin-23 ; Interleukin-5 ; Interleukins ; Monocytes ; Mucous Membrane ; Nasal Polyps ; Passive Cutaneous Anaphylaxis ; Population Characteristics ; Principal Component Analysis ; Rhinitis ; Sinusitis ; Up-Regulation ; Vascular Cell Adhesion Molecule-1

OBJECTIVES: To study the expression of interleukin-17A (IL-17A) in the serum of children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and its clinical significance. METHODS: A total of 143 children with KD who were hospitalized in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2021 to June 2022 were enrolled in this prospective study, among whom 115 had IVIG-sensitive KD and 28 had IVIG-resistant KD. After matching for sex and age, 110 children with acute respiratory infectious diseases (fever time ≥5 days but without KD) were enrolled as the control group. The enzyme-linked immunosorbent assay was used to measure the serum level of IL-17A. The levels of white blood cell count (WBC), neutrophil count (NE), platelet count, erythrocyte sedimentation rate, and C-reactive protein (CRP) were measured. The receiver operating characteristic curve was plotted to analyze the value of WBC, NE, CRP, and IL-17A in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis was used to evaluate the predictive factors for resistance to IVIG in children with KD. RESULTS: Before IVIG treatment, the KD group had a significantly higher serum level of IL-17A than the control group (P<0.05), and the children with IVIG-resistant KD had a significantly higher serum level of IL-17A than those with IVIG-sensitive KD (P<0.05). The receiver operating characteristic curve analysis showed that WBC, NE, CRP, and IL-17A had an area under the curve of 0.718, 0.741, 0.627, and 0.840, respectively, in the prediction of IVIG-resistant KD. With serum IL-17A ≥44.06 pg/mL as the cut-off value, IL-17A had a sensitivity of 84% and a specificity of 81% in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis showed that a high serum level of IL-17A was a predictive factor for resistance to IVIG in children with KD (OR=1.161, P=0.001). CONCLUSIONS Serum IL-17A levels are elevated in children with IVIG-resistant KD, and serum IL-17A level (≥44.06 pg/mL) may have a predictive value for resistance to IVIG in children with KD.
Humans ; Child ; Infant ; Aged, 80 and over ; Immunoglobulins, Intravenous/therapeutic use* ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Interleukin-17 ; Clinical Relevance ; Prospective Studies ; C-Reactive Protein/analysis* ; Retrospective Studies

OBJECTIVETo investigate the percentages of peripheral blood γδ T cells and regulatory T cells (Treg) and the expression of associated cytokines, interleukin 17 (IL-17) and transforming growth factor-β1 (TGF-β1), in infants with human cytomegalovirus (HCMV) infection.

METHODSTwenty-two infants with HCMV infection (HCMV group) and 22 healthy infants who underwent physical examination (control group) were enrolled in this study. The percentages of peripheral blood γδ T cells and Treg cells were determined by flow cytometry. The levels of IL-17 and TGF-β1 in plasma were measured using ELISA.

RESULTSCompared with the control group, the HCMV group had significantly higher percentage of γδ T cells and IL-17 level (P<0.01) and significantly lower percentage of Treg cells and TGF-β1 level (P<0.01). In the HCMV group, the percentage of γδ T cells was negatively correlated with the percentage of Treg cells and TGF-β1 level (P<0.05), but positively correlated with IL-17 level (P<0.05); the percentage of Treg cells was positively correlated with TGF-β1 level (P<0.05), but negatively correlated with IL-17 level (P<0.05); there was no correlation between IL-17 level and TGF-β1 level (P>0.05).

CONCLUSIONSThere is an imbalance between γδ T cells and Treg cells in the peripheral blood of infants with HCMV infection, and γδ T cells may be involved in the secretion of IL-17.

Cytokines ; blood ; Cytomegalovirus Infections ; immunology ; Female ; Humans ; Infant ; Interleukin-17 ; blood ; Male ; Receptors, Antigen, T-Cell, gamma-delta ; analysis ; T-Lymphocytes, Regulatory ; immunology ; Transforming Growth Factor beta1 ; blood

The sequestration of infected erythrocytes in the placenta can activate the syncytiotrophoblast to release cytokines that affect the micro-environment and influence the delivery of nutrients and oxygen to fetus. The high level of IL-10 has been reported in the intervillous space and could prevent the pathological effects. There is still no data of Th17 involvement in the pathogenesis of placental malaria. This study was conducted to reveal the influence of placental IL-17 and IL-10 levels on fetal weights in malaria placenta. Seventeen pregnant BALB/C mice were divided into control (8 pregnant mice) and treatment group (9 pregnant mice infected by Plasmodium berghei). Placental specimens stained with hematoxylin and eosin were examined to determine the level of cytoadherence by counting the infected erythrocytes in the intervillous space of placenta. Levels of IL-17 and IL-10 in the placenta were measured using ELISA. All fetuses were weighed by analytical balance. Statistical analysis using Structural Equation Modeling showed that cytoadherence caused an increased level of placental IL-17 and a decreased level of placental IL-10. Cytoadherence also caused low fetal weight. The increased level of placental IL-17 caused low fetal weight, and interestingly low fetal weight was caused by a decrease of placental IL-10. It can be concluded that low fetal weight in placental malaria is directly caused by sequestration of the parasites and indirectly by the local imbalance of IL-17 and IL-10 levels.
Animals ; Female ; *Fetal Weight ; Humans ; Interleukin-10/*analysis/metabolism ; Interleukin-17/*analysis/metabolism ; Malaria/*metabolism/parasitology/physiopathology ; Male ; Mice ; Mice, Inbred BALB C ; Placenta/*chemistry/metabolism ; Plasmodium berghei/*physiology ; Pregnancy ; Pregnancy Complications, Parasitic/*metabolism/parasitology/physiopathology