IL-10 AND IL-35 AS INFLAMMATION REGULATORS IN PATIENTS WITH ALLERGIC RHINITIS AND MILD ATOPIC ASTHMA

Background. Significantly less is known about the immunoregulative cytokines, especially in allergic airway disease. This study aims to present the involvement of IL-35 and IL-10 in patients with allergic rhinitis (AR) and allergic bronchial asthma (BA). Methodology. The study comprised 71 patients –AR, patients with concomitant AR and mild atopic BA, and healthy controls (HC). We examined the serum levels of IL-35 and IL-10, along with other instrumental examinations, between March and September 2021. Findings. Levels of the regulatory cytokines IL-35 and IL-10 were significantly lower in patients than in HC (87.19±11.90 vs. 96.12±1.79 pg/ml; and 30.26±17.55 vs. 111.56±65.03 pg/ml, respectively). Furthermore, threefold higher serum IL-10 levels were found in healthy subjects compared to patients (p = 0.006). No difference in the levels of interleukins was found between the studied groups. Conclusions. Our results indicate that elevated IL-35 and IL-10 may play an essential role in reducing the activity of underlying allergic inflammation in allergic respiratory diseases, although no difference in the levels of the studied cytokines was found between the different groups of patients. Therefore, we can speculate that the immunosuppressive cytokines IL-35 and IL-10 were involved in maintaining the healthy state of no inflammation.

Effectiveness and safety of oral lactococci-based vaccine encoding triple common allergens to prevent airway allergy in mice

Allergic airway disease is the most common chronic airway inflammatory disorder in developed countries. House dust mite, cockroach, and mold are the leading allergens in most tropical and subtropical countries, including Taiwan. As allergen avoidance is difficult for patients allergic to these perennial indoor allergens, allergen-specific immunotherapy (ASIT) is the only available allergen-specific and disease-modifying treatment. However, for patients sensitized to multiple allergens, ASIT using each corresponding allergen is cumbersome. In the present study, we developed a recombinant L. lactis vaccine against the three most common indoor aeroallergens and investigated its effectiveness for preventing respiratory allergy and safety in mice. Three recombinant clones of Der p 2 (mite), Per a 2 (roach), and Cla c 14 (mold) were constructed individually in pNZ8149 vector and then electroporated into host strain L.lactis NZ3900. BALB/c mice were fed with the triple vaccine 5 times per week for 4 weeks prior to sensitization. The effectiveness and safety profile were then determined. Oral administration of the triple vaccine significantly alleviated allergen-induced airway hyper-responsiveness in the vaccinated mice. The allergen-specific IgG2a was upregulated. IL-4 and IL-13 mRNA expressions as well as inflammatory cell infiltration in the lungs decreased significantly in the vaccinated groups. No body weight loss or abnormal findings in the liver and kidneys were found in any of the groups of mice. This is the first report to describe a triple-aeroallergen vaccine using a food-grade lactococcal expression system. We developed a convenient oral delivery system and intend to extend this research to develop a vaccination that can be self-administered at home by patients.

Colonic Mucosal Immune Activation in Mice with Ovalbumin-Induced Allergic Airway Disease: Association between Allergic Airway Disease and Irritable Bowel Syndrome

Recent studies on the pathophysiology of irritable bowel syndrome (IBS) have focused on the role of mast cells (MCs) in intestinal mucosal immunity. A link between allergic airway diseases (AADs) and IBS has been suggested because both diseases have similar pathophysiology. We aimed to investigate whether the induction of AAD in mice could lead to inflammation of the colonic mucosa, similar to IBS. We also evaluated whether this inflammatory response could be suppressed by administering a therapeutic agent. Mice were divided into three groups: control, AAD-induced, and salbutamol-treated. An AAD mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin. Mice with AAD were intranasally administered salbutamol. Analyses of cytokine levels, MC count, and tryptase levels in the intestinal mucosa were performed to compare the changes in inflammatory responses among the three groups. Inflammation was observed in the intestinal mucosa of mice in the AAD group. This inflammation in AAD mice was suppressed after salbutamol treatment. Our study demonstrates that AAD induces an inflammatory response similar to that in IBS, suggesting a possible association between IBS and AADs. In patients with IBS with such allergic components, salbutamol may have the potential to alleviate the inflammatory response.

Study The Anti-Asthmatic Activity of Guggulsterone In Ovalbumin-Induced Asthma In Rat

Asthma is a chronic in?ammatory respiratory disease associated with the changes of asthmatic airway structural that result from interact remodeling and in?ammatory processes lead to obstruction of airway. Guggulsterone (GS) is a bioactive compound and plant steroid present in guggul gum of Commiphora wightii, which has anti-inflammatory and antioxidant activities. This study designed to investigate of anti-inflammatory activity of gugglsterone in improvement of asthma. Forty eight healthy albino male rats divided to six groups, Group I: Control group (distal water), Group II: Positive control group (distal water) with sensitization, Group III: Guggulsterone (25 mg/kg/day) with sensitization, Group IV: Guggulsterone (50 mg/kg/day) with sensitization, Group V: Prednisolone (4.12 mg/kg/day) with sensitization, Group VI: Guggulsterone (50mg/kg/day) without sensitization. Rats were sacrificed and blood samples were collected to prepare of serum samples that used in ELISA kits for measuring of IL-4, IL-5, IL-33, TNF IgE. In addition, WBC counts in Bronchoalveolar lavage fluid. ALL parameters (IL-4, IL-5, IL-33, TNF, & IgE) levels for rats of treated groups with gugglsterone were significant (P<0.05) reduced in compared to sensitized group. Similarly, WBC count for rats treated groups with guggulsterone was significantly (P<0.05) fewer than sensitized group. In conclusion, our results provide a clue that guggulsterone has a potent anti-inflammatory activity that improved OVA-induced asthma and is useful for the preventive of allergic airway disease in rodents.

Matricellular Protein Periostin Promotes Pericyte Migration in Fibrotic Airways

Introduction: Periostin is a matricellular protein that is currently used as a biomarker for asthma. However, its contribution to tissue remodeling in allergic asthma is currently unknown. We have previously demonstrated that tissue-resident mesenchymal stem cells known as pericytes are a key cell type involved in airway remodeling. This is thought to be caused the uncoupling of pericytes from the microvasculature supporting the large airways, facilitated by inflammatory growth factors and cytokines. It is hypothesized that periostin may be produced by profibrotic pericytes and contribute to the remodeling observed in allergic asthma.Methods: Lung sections from mice with allergic airway disease driven by exposure to house dust mite (HDM) were stained using an anti-periostin antibody to explore its involvement in fibrotic lung disease. Human pericytes were cultured in vitro and stained for periostin to assess periostin expression. Migration assays were performed using human pericytes that were pretreated with TGF-β or periostin. ELISAs were also carried out to assess periostin expression levels in bronchoalveolar lavage fluid as well as the induction of periostin production by IL-13.Results: Immunostaining indicated that pericytes robustly express periostin, with increased expression following treatment with TGF-β. Migration assays demonstrated that pericytes treated with periostin were more migratory. Periostin production was also increased in HDM exposed mice as well as in cultured pericytes treated with IL-13.Conclusion: Periostin is produced by pericytes in response to TGF-β or IL-13, and periostin plays a key role in inducing pericyte migration. The increase in periostin expression in TGF-β or IL-13 treated pericytes suggests that IL-13 may trigger periostin production in pericytes whilst TGF-β modulates periostin expression to promote pericyte migration in the context of tissue fibrosis.

A Helminth-Derived Chitinase Structurally Similar to Mammalian Chitinase Displays Immunomodulatory Properties in Inflammatory Lung Disease

Immunomodulation of airway hyperreactivity by excretory-secretory (ES) products of the first larval stage (L1) of the gastrointestinal nematode Trichuris suis is reported by us and others. Here, we aimed to identify the proteins accounting for the modulatory effects of the T. suis L1 ES proteins and studied six selected T. suis L1 proteins for their immunomodulatory efficacy in a murine OVA-induced allergic airway disease model. In particular, an enzymatically active T. suis chitinase mediated amelioration of clinical signs of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung, the associated chemokines, and increased numbers of RELMα+ interstitial lung macrophages. While there is no indication of T. suis chitinase directly interfering with dendritic cell activation or antigen presentation to CD4 T cells, treatment of allergic mice with the worm chitinase influenced the hosts’ own chitinase activity in the inflamed lung. The three-dimensional structure of the T. suis chitinase as determined by high-resolution X-ray crystallography revealed high similarities to mouse acidic mammalian chitinase (AMCase) but a unique ability of T. suis chitinase to form dimers. Our data indicate that the structural similarities between the parasite and host chitinase contribute to the disease-ameliorating effect of the helminth-derived chitinase on allergic lung inflammation.