leptin and Rhinitis--Allergic

Since the leptin participates in the upregulation of type 2 innate lymphoid cells (ILC2s). We investigated the role of the leptin/ILC2 axis in AR pathogenesis in Chinese paediatric patients with obesity.. Seventy AR paediatric patients with or without obesity and 30 healthy obese subjects were enrolled. The levels of leptin, its receptor and ILC2 milieu were measured, and correlations between them and clinical symptom severity and between ILC2 milieu and leptin levels were assessed. Changes of ILC2 milieu in AR patients after leptin stimulation were also detected.. Levels of leptin, its receptor and ILC2 milieu levels were significantly higher in the disease than in the controls, and highest in the obese-AR group. The leptin/ILC2 axis and severity of clinical symptoms in obese patients with AR were significantly correlated, similarly to what was observed between leptin/leptin receptors and ILC2 milieu. Recombinant leptin could significantly increased the levels of ILC2 milieu in the obese-AR group.. These findings suggest the unique function ofthe leptin/ILC2 axis in obese paediatric AR patients. The mechanism by which obesity promotes AR in paediatric patients may be related to the leptin/ILC2 axis.

Topics: Child; Cytokines; Humans; Immunity, Innate; Leptin; Lymphocytes; Pediatric Obesity; Rhinitis, Allergic

Objective To observe the impact of leptin on the activation of group 2 innate lymphocytes (ILC2) in obese adult patients with allergic rhinitis (AR), and investigate its role and significance in the pathogenesis of AR. Methods A total of 70 patients with AR were enrolled in the study and divided into obese AR group and non-obese AR group according to body mass index (BMI), and matched with 30 cases in the healthy control group with no difference in age and gender during the same period. Flow cytometry was used to detect the ratio of ILC2 in peripheral blood mononuclear cells (PBMCs) of each group, real-time quantitative PCR to detect the expression of leptin mRNA, and ELISA to detect the serum leptin. The correlation between leptin and ILC2 was analyzed, and the changes in the ratio of ILC2 and relevant immune indexes in PBMCs of the AR group before and after the intervention of recombinant leptin were observed. Results Compared with healthy control group, the expressions of leptin and ILC2 of the AR group increased significantly, and the level of the obese AR group was significantly higher than that of the non-obese AR group. The expressions of leptin and ILC2 in the obese AR group were positively correlated in a significant manner. After the intervention of recombinant leptin, the ILC2 level of the obese AR group increased significantly. Conclusion The pathogenesis of AR in obese adults is related to its high expression of leptin, and the activation of ILC2 mediated by leptin aggravates its pathogenetic process.

Topics: Adult; Humans; Immunity, Innate; Leptin; Leukocytes, Mononuclear; Lymphocytes; Obesity; Rhinitis, Allergic

Obesity/overweight is associated with a higher risk of allergic rhinitis (AR) in children.. This study aimed at exploring the mechanisms by which obesity affects the severity of AR through leptin and interleukin (IL)-1β were investigated.. In all, 210 subjects with AR and 82 subjects without AR were included in this study. The levels of leptin and inflammatory biomarkers were measured in the serum to investigate the correlation with the severity of AR. Additionally, we analyzed whether changes in BMI regulate the severity of AR through serial follow-up of obese children.. IL-1β, which is a biomarker of active inflammation in AR, was significantly higher in individuals with AR than in those without and higher in subjects in the obesity group than in those in the normal weight group. A regression analysis showed that the leptin level was associated with increased IL-1β expression in children with AR. In the multivariate analysis, only parental AR (9.2-fold increase in risk), elevated leptin (11.3-fold increase in risk), and high expression of IL-1β (5.8-fold increase in risk) emerged as significant risk factors of moderate to severe persistent allergic rhinitis. We also found that children with an increase or decrease in BMI showed changes in IL-1β and AR symptoms, which these changes were dependent on leptin and BMI.. These results suggest that obesity is an important risk factor for the exacerbation of symptoms and leptin can exacerbate inflammation as well as severe and persistent symptoms through IL-1β in AR.

Topics: Biomarkers; Child; Disease Progression; Disease Susceptibility; Humans; Interleukin-1beta; Leptin; Pediatric Obesity; Rhinitis, Allergic; Risk Factors; Severity of Illness Index

Leptin may play a critical role in airway inflammation. However, it has rarely been evaluated in rhinitis with different aetiology. This study aimed to compare the serum leptin levels between allergic rhinitis (AR) and nonallergic rhinitis (NAR).. Patients with chronic rhinitis were classified due to skin prick (ALK-Abello/Madrid) and/or serum-specific immunoglobulin E tests (UniCAP 100-Pharmacia), against to aeroallergens if concordant with symptoms.. A total of 398 patients with a mean age of 29.03 years were recruited and grouped as AR and NAR. Mean serum leptin levels were similar in patients with NAR and AR, as well as in patients with and without asthma, but were significantly higher in females than males in both groups. Also, leptin levels were significantly higher in obese than nonobese patients in AR. In correlation analysis, leptin levels were found to be correlated with female gender, older age, and high body mass index (BMI) in the whole group. Despite the higher total nasal symptom score (TNSS) in patients with AR compared with NAR, there was no association of leptin levels with TNSS, severity and seasonality of symptoms, and allergen sensitization. In logistic regression analysis, younger age and high serum leptin levels were found to be independent predictors for the diagnosis of AR.. We conclude that female patients with high BMI are more prone to AR probably due to immunological effects of adipose tissue, in addition to hormonal factors. This study showed that leptin measurement has limited value as a sole diagnostic tool to differentiate AR and NAR.

Topics: Adult; Allergens; Female; Humans; Immunoglobulin E; Leptin; Male; Rhinitis; Rhinitis, Allergic

Recent studies suggest that leptin is involved in Th2 response in allergic rhinitis (AR). However, the effect of leptin on type II innate lymphoid cells (ILC2s) in AR is not well characterized.. Twenty-six AR patients and 20 healthy controls were enrolled. Serum leptin levels were measured, and their correlation with ILC2 and type II cytokines were analyzed using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. ILC2 differentiation and cytokine production stimulated by human recombinant leptin were analyzed by real-time polymerase chain reaction (PCR) and ELISA. AR mouse models were also established to verify the effect of leptin on ILC2 cell regulation.. Our results showed that elevated serum leptin in AR patients was correlated with the percentage of ILC2 and the expression of type II cytokines. The recombinant leptin enhanced the expression of ILC2 cell transcription factors and type II cytokine through the PI3K/AKT pathway. The AR mice treated with leptin showed as stronger ILC2 inflammation and symptoms compared with control mice.. Our data provide evidence that upregulation of leptin promotes ILC2 responses in AR and this process was achieved through the PI3K/AKT pathway.

Topics: Adolescent; Adult; Animals; Blotting, Western; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Humans; Leptin; Male; Mice, Inbred BALB C; Middle Aged; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Real-Time Polymerase Chain Reaction; Rhinitis, Allergic; Young Adult

Interleukin-17 plays important roles in allergic diseases. Several studies proved that leptin promoted Th17 immune responses by inducing ROR. Fifteen AR patients and fifteen healthy controls were enrolled. Serum leptin levels were measured, and their correlation with the frequency of IL-17+ ILC2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. ILC2 was stimulated by leptin, and the expression of IL-17, IL-5, and IL-13 was detected by ELISA. The correlated pathways were confirmed by real-time PCR.. We found that serum leptin and the frequency of IL-17-producing ILC2s in AR were significantly higher compared with those in controls. After being incubated with leptin, the frequency of IL-17+ ILC2 cells and IL-17 production from ILC2 was upregulated compared with that in controls. We also found that leptin induced ROR. Our data provide preliminary evidence that leptin-induced IL-17 production from ILC2 cells is dependent on ROR

Topics: Adaptive Immunity; Adult; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Humans; Immunity, Innate; Interleukin-17; Leptin; Male; Middle Aged; Rhinitis, Allergic; Young Adult

Allergic rhinitis is characterized by a remodeling of nasal epithelium. Since the Notch and TGF-β signaling pathways are known to be involved in cell differentiation and remodeling processes and leptin adipokine has already been identified as a marker for homeostasis in human bronchial and nasal epithelial cells of asthmatics, roles played by these pathways have been investigated for chronic allergic rhinitis.. The leptin/leptin receptor expression has been investigated in a study with 40 biopsies from allergic (AR, n = 18) and non-allergic (C, n = 22) inferior turbinates, using immunohistochemistry, immunofluorescence staining and RT-PCR. In addition, extracts from in vitro samples prepared from primary cells of inferior turbinates as well as in vitro cultured human nasal epithelial RPMI 2650 cells (ATCC-CCL-30) were also tested for leptin expression and activation of the Notch-1 pathway.. With regards to AR, in vivo expression levels of both leptin and its receptor significantly decreased in comparison to C. Furthermore, leptin receptor mRNA was significantly reduced in AR as compared to C. Immunofluorescence showed an apparent co-expression of leptin receptor with Notch-1, which was not seen with TGF-β. In vitro, in primary turbinate epithelial cells, the expression of leptin receptor and Notch-1 significantly decreased in AR as compared to C. Moreover, in RPMI 2650 cells, leptin receptor expression was shown to be induced by Notch-1 ligand signaling.. Thus, both the leptin and Notch-1 pathways appear to represent markers for epithelial homeostasis in allergic rhinitis.

Topics: Adult; Biopsy; Case-Control Studies; Cell Line; Epithelial Cells; Female; Gene Expression Regulation; Homeostasis; Humans; Leptin; Male; Middle Aged; Nasal Mucosa; Primary Cell Culture; Receptor, Notch1; Receptors, Leptin; Rhinitis, Allergic; RNA, Messenger; Signal Transduction; Transforming Growth Factor beta1; Turbinates

The prevalence of both obesity and allergic diseases in children has increased over the last several decades. However, the direct relationship between diverse allergic diseases and obesity has varied in different studies. Therefore, we aimed to examine the effect of obesity on the incidence and severity of allergic rhinitis (AR) and the possible key inflammation mediators during AR.. A total of 3126 healthy students (without chronic diseases) were recruited from 14 randomly selected secondary schools in Guangzhou, China. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHR), and body fat percentage (PBF) were measured and compared. The effect of obesity indicators and leptin level (exposures) on the incidence (primary outcome) and severity of AR (secondary outcomes) was analyzed. Inflammatory markers were detected and compared among groups.. The symptom score (9.5 ± 3.1 vs 8.2 ± 3.5, P < .05) and medication score (3.6 ± 1.6 vs 2.9 ± 1.8, P < .05) were significantly higher in obese children with AR than in non-obese children with AR. After adjusting for potential confounders, multiple linear regression analysis showed that the serum leptin concentration was significantly correlated with the levels of T-helper (TH) 2 cytokines (coefficient, 0.48 [95% CI, 0.05-0.91]), TH17 cytokines (coefficient, 0.39 [95% CI, 0.11-0.89]), and regulatory T-cell cytokines (IL-10, coefficient, -0.43 [95% CI, -0.02-0.65]; TGF-β, coefficient, -0.65 [95% CI, -0.06-1.35]) in patients with AR.. Our study shows that obesity exacerbates inflammation and contributes to disease severity in AR. Our study provides evidence that leptin was involved in enhanced TH inflammation as well as the accumulation and activation of inflammatory cells in obese children with AR.

Topics: Anthropometry; Asian People; Child; China; Cross-Sectional Studies; Cytokines; Female; Humans; Incidence; Leptin; Lipids; Male; Pediatric Obesity; Rhinitis, Allergic; Severity of Illness Index

Recent studies suggest that T helper 17 (Th17) cell subset, a distinct pro-inflammatory CD4 +  T cell lineage, may play an important role in the pathophysiology of allergic rhinitis (AR). However, the regulation of Th17 response in allergic disease is not well characterized.. Thirty AR and 30 healthy children were enrolled. Serum leptin and OPN levels were measured, and their correlation with IL-17 expression was analyzed using enzyme-linked immunosorbent assay (ELISA). Th17 cell differentiation and cytokine production in peripheral blood mononuclear cell (PBMCs) stimulated by leptin and OPN and related inhibitors were analyzed by ELISA. AR mice models were also established to verify the effect of leptin and OPN on Th17 cell regulation. Immunoprecipitation was performed to explore the interaction between OPN and leptin in Th17 cells.. Our results showed that elevated serum leptin and OPN in AR children were correlated with serum IL-17 level (r = .53, P < .01). The recombinant leptin and OPN enhanced Th17 responses from PBMCs synergistically through nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathway and β3 integrin receptor. The AR mice showed as more severe Th17 responses and symptoms compared with control mice. Immunoprecipitation showed that OPN and leptin may interact with each other directly, and this process may be mediated by β3 integrin.. Our data provide evidence that upregulation of leptin and OPN promotes Th17 responses in AR, and this process may be achieved through NF-κB, MAPK, and JNK pathway and β3 integrin.

Topics: Animals; Cell Differentiation; Child; Child, Preschool; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoprecipitation; Leptin; Leukocytes, Mononuclear; Male; Mice; Mice, Inbred BALB C; Osteopontin; Rhinitis, Allergic; Signal Transduction; Th17 Cells

Increasing evidence suggests that leptin is upregulated during allergic reactions in the airway and related to the severity of disease in allergic rhinitis (AR). In this study, we aimed to investigate the expression of leptin during sublingual immunotherapy (SLIT) in AR patients.. Forty AR patients without obesity were recruited in this study. Twenty patients received house dust mite (HDM) allergen extract for SLIT and twenty patients received placebo randomly. Protein expression of leptin in serum and nasal lavage was tested by enzyme-linked immuno sorbent assay (ELISA) 1 and 2 years after SLIT treatment, respectively. Peripheral blood mononuclear cells (PBMCs) and human nasal epithelial cell were prepared and stimulated by recombinant leptin after 24 months' SLIT treatment and the induction of Th2 cytokines (IL-4/IL-5/IL-13) were detected by ELISA.. SLIT treatment decreased the expression of leptin protein in serum and nasal lavage significantly compared with placebo group 1 and 2 years after SLIT treatment. Nasal leptin level was correlated to decreased Th2 response (IL-4/IL-5/IL-13) and enhanced Treg (IL-10/TGF-beat) response after 2 years' SLIT. We also found that SLIT decreased the ability of leptin in promoting Th2 cytokines expression by PBMCs and human nasal epithelial cell after 2 years' SLIT treatment.. Changes of leptin expression in serum and nasal lavage may be correlated with Th2/Treg regulation during SLIT. Our results suggested that leptin served as an important biomarker during SLIT.

Topics: Adolescent; Adult; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Middle Aged; Recombinant Proteins; Rhinitis, Allergic; Sublingual Immunotherapy; Treatment Outcome; Young Adult

Allergic rhinitis (AR) is characterized by tissue and blood eosinophilia. Previous studies showed enhanced eosinophilia in allergic rhinitis patients with obesity, suggesting an association between obesity and eosinophilia. However, the interaction and mechanism between obesity and eosinophilia is still unclear.. We recruited thirty AR children and 30 controls in this study. Expression of leptin and osteopontin (OPN) proteins in serum was detected, and correlation analysis with eosinophilia was performed. The effect of leptin or OPN on eosinophil apoptosis, adhesion, migration, and activation of eosinophil was examined. Ovalbumin-sensitized mice were established to prove the role of obesity on eosinophil regulation by leptin and OPN.. We found that upregulated serum and nasal leptin and OPN expression in AR were positively correlated with eosinophilia and eosinophil cationic protein levels. Leptin or OPN inhibited eosinophil apoptosis, demonstrated as inhibited DNA fragmentation and phosphatidylserine (PS) redistribution (. Our results suggested that in an obese state, upregulation of leptin and OPN regulates apoptosis, adhesion, migration, and activation of eosinophils, and this process may be mediated by the PI3K and anti-

Topics: Animals; Apoptosis; Cell Adhesion; Cell Death; Cell Movement; Cells, Cultured; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Eosinophil Cationic Protein; Eosinophils; Female; Humans; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Osteopontin; Rhinitis, Allergic

Leptin is involved in the lung epithelial homeostasis. Its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure leading to consequential structural abnormalities in the nasal epithelium. Topical corticosteroids are recommended as first-line therapy in AR. Parietaria pollen is one of the most important allergenic sources in the southern Europe. In vitro, in human nasal epithelial cell line RPMI 2650, we aimed to determine whether allergen stimulation acts on leptin/leptin receptor pathway and how fluticasone furoate (FF) influences this pathway. The effects of the major allergen recombinant Par j 1 (rPar j 1), of FF, of leptin, and of TGF-β1 on cell proliferation, on leptin/leptin receptor expression and modulation (by clonogenic test, by RT-q-RT-PCR, by immunocytochemistry and by flow-cytometry), and on STAT-3 activation (assessing nuclear translocation by western blot analysis) were assessed. We found that rPar j 1 and TGF-β1 significantly decreased cell proliferation and down-regulated the leptin/leptin receptor pathway, whereas FF and leptin reverted them, both alone and in combination. Furthermore, rPar j 1 reduced, while leptin and FF increased STAT-3 activation. In conclusion, FF and leptin itself are able to preserve nasal epithelial homeostasis restoring the leptin/leptin receptor pathway altered by rPar j 1 exposure.

Topics: Allergens; Androstadienes; Cell Line; Cell Proliferation; Homeostasis; Humans; Leptin; Nasal Mucosa; Plant Proteins; Protein Transport; Receptors, Leptin; Recombinant Proteins; Rhinitis, Allergic; Signal Transduction; STAT3 Transcription Factor; Transforming Growth Factor beta1