Mepolizumab as a steroid-sparing treatment option in a patient with eosinophilic granulomatosis with polyangiitis / Mepolizumabe como terapêutica poupadora de esteroides num paciente com granulomatose eosinofílica com poliangiite

Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem disorder characterized by asthma, peripheral blood eosinophilia, and signs of vasculitis. Glucocorticoids are considered the cornerstone of treatment, but most patients remain steroid-dependent and carry a significant burden of adverse effects. We report a case of a patient with steroid-dependent EGPA successfully treated with mepolizumab. A 36-year-old man presented with persistent rhinitis, dyspnea, wheezing, and dry cough poorly controlled with inhaled therapy. Eosinophilia in peripheral blood and bronchoalveolar lavage fluid was seen. Histological findings from nasal mucosa revealed eosinophilic microabscesses and vasculitis without granulomas compatible with EGPA diagnosis. After daily oral prednisolone (PSL) was started, symptoms and eosinophilia improved, but adverse effects emerged. Attempts at tapering off PSL resulted in worsening of symptoms. He started mepolizumab 300 mg monthly, with clinical improvement and sustained disease remission, which allowed reducing the need for PSL. We present a very disabling steroiddependent EGPA. Mepolizumab was able to taper off PSL while maintaining symptomatic control.

Granulomatose eosinofílica com poliangiite (EGPA) é uma doença multissistêmica caracterizada por asma, eosinofilia no sangue periférico e sinais de vasculite. Os corticoides são considerados a base do tratamento, no entanto, a maioria dos pacientes permanece dependente deste tratamento com os seus efeitos adversos associados. Relatamos o caso de um paciente com granulomatose eosinofílica dependente de esteroides com poliangiite (EGPA) tratado com sucesso com mepolizumabe. Um homem de 36 anos apresentou rinite persistente, dispneia, sibilos e tosse seca mal controlada com terapia inalada. Observou-se eosinofilia no sangue periférico e no lavado broncoalveolar. Os achados histológicos da mucosa nasal revelaram microabscessos eosinofílicos e vasculite sem granulomas compatíveis com o diagnóstico de EGPA. Após o início da prednisolona oral diária (PSL), os sintomas e a eosinofilia melhoraram, mas surgiram efeitos adversos. As tentativas de redução gradual da PSL resultaram no agravamento dos sintomas. Iniciou mepolizumabe 300 mg mensalmente, com melhora clínica e remissão sustentada da doença, o que permitiu reduzir a necessidade de PSL. Apresentamos um EGPA dependente de esteroides muito incapacitante. O mepolizumab foi capaz de diminuir o PSL mantendo o controle sintomático sustentado.

Pharmacokinetics of Sinapic Acid from Stir-fried Raphani Semen in Rats and Its PK-PD Correlation Analysis / 中国实验方剂学杂志

Objective::To study the pharmacokinetics of sinapic acid from stir-fried Raphani Semen in normal rats and the correlation between pharmacokinetics-pharmacodynamics (PK-PD) in asthma rats. Method::Normal rats received 4.5, 9, 18 g·kg-1 of stir-fried Raphani Semen by oral administration, respectively. Blood was taken from ophthalmic venous plexus at different time points according to the experimental design, the plasma concentration of sinapic acid was analyzed by UHPLC-MS/MS, and data analysis was performed using DAS 3.2.8 software to obtain the pharmacokinetic parameters. Rat asthma model was established by intraperitoneal injection of ovalbumin with aluminum hydroxide, and treated with ethanol extract of stir-fried Raphani Semen (low and high doses of 4.5, 9 g·kg-1). After treatment for 3 weeks, taking blood at different time points, plasma and serum were separated. UHPLC-MS/MS was established for the determination of plasma concentration of sinapic acid, contents of interleukin-5 (IL-5), immunoglobuin E (IgE), tumor necrosis factor-α (TNF-α) in serum at different time points were detected by enzyme-linked immunosorbent assay (ELISA), DAS 3.2.8 software was used for PK-PD model fitting and data analysis. Result::After normal rats were administrated with low, medium and high doses of stir-fried Raphani Semen, the peak concentration (Cmax) of sinapic acid in plasma were (29.35±10.32), (62.70±27.47), (137.33±40.95) μg·L-1, its area under the curve (AUC0-t) were (92.83±27.16), (240.74±75.09), (633.95±195.88) μg·L-1·h, its peak time (Tmax) were (2.58±0.80), (3.00±0), (5.50±1.23) h, respectively. Compared with the low dose group, AUC0-t and mean retention time (MRT0-t) were all increased in the medium and high dose groups, showing statistical differences (P<0.05, P<0.01). The linear relationship of AUC0-t in sinapic acid was good within the dose range of 4.5-18 g·kg-1. After treating with ethanol extract of stir-fried Raphani Semen for 0.083, 0.167 h, compared with the model group of asthmatic rats, serum levels of IL-5, IgE, TNF-α of the medication groups were decreased to different degrees (P<0.05, P<0.01). Cmax of sinapic acid in the low and high dose groups were (58.43±29.94), (61.16±18.79) μg·L-1, its AUC0-t were (188.75±37.07), (247.90±36.89) μg·L-1·h, respectively. AUC0-t, apparent volume of distribution (Vz/F) and clearance rate (CLz/F) all increased significantly with the increase of dose. The best pharmacokinetic model of sinapic acid was fitted as a one-compartment model for extravascular administration, PK-PD model may be applicable to indirect connection model. Conclusion::The plasma concentration of sinapic acid is correlated with contents of IL-5, IgE and TNF-α, dosage and functional state (pathological or physiological state) can affect the pharmacokinetic behavior of sinapic acid from stir-fried Raphani Semen in rats, and it has a certain correlation with the anti-asthmatic effect.

Mepolizumabe na doença respiratória exacerbada por aspirina - DREA / Mepolizumab in aspirin-exacerbated respiratory disease - AERD

Relato de caso que ilustra a eficácia e a segurança do uso do mepolizumabe na doença respiratória exacerbada por aspirina (DREA). A utilização de anticorpo monoclonal no tratamento desta doença respiratória de difícil tratamento tem possibilitado o controle da inflamação crônica e o maior conhecimento sobre a fisiopatogenia da doença.

This case report shows the efficacy and safety of mepolizumab in aspirin-exacerbated respiratory disease (AERD). The use of monoclonal antibodies in the treatment of this severe disease has provided improved control of chronic inflammation and greater understanding about the pathophysiology of the disease.

Efficacy and Safety of Benralizumab for Korean Patients With Severe, Uncontrolled Eosinophilic Asthma

PURPOSE: In the Phase III SIROCCO trial (NCT01928771), benralizumab significantly reduced asthma exacerbations and improved lung function and symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate efficacy and safety of benralizumab for Korean patients in SIROCCO. METHODS: SIROCCO was a randomized, double-blind, parallel-group, placebo-controlled trial of 1,204 patients aged 12–75 years with severe asthma uncontrolled by high-dosage inhaled corticosteroids/long-acting β2-agonists (ICS/LABA). Patients received benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W; first 3 doses Q4W) or placebo Q4W for 48 weeks. The primary analysis population comprised patients with blood eosinophil counts ≥ 300 cells/µL. This subgroup analysis evaluated Korean patients from this group. RESULTS: Of 122 Korean patients randomized, 86 had blood eosinophil counts ≥ 300 cells/µL. Benralizumab reduced the annual asthma exacerbation rate by 70% (Q4W: rate estimate 0.79, rate ratio 0.30 [95% confidence interval {CI}, 0.13–0.65], nominal P = 0.003; n = 28) and 85% (Q8W: rate estimate 0.40, rate ratio 0.15 [95% CI, 0.06–0.36], nominal P < 0.001; n = 30) vs. placebo (rate estimate 2.67, n = 28). Prebronchodilator forced expiratory volume in 1 second was increased with benralizumab treatment by 0.270 L (Q4W: 95% CI, 0.039–0.500, nominal P = 0.023; n = 28) and 0.362 L (Q8W: 95% CI, 0.143–0.582, nominal P = 0.002; n = 30) vs. placebo (n = 27). Total asthma symptom score was similar for patients receiving either benralizumab Q4W (−0.27 [95% CI, −0.83 to 0.30], nominal P = 0.356; n = 27) or benralizumab Q8W (0.10 [95% CI, −0.44 to 0.65], nominal P = 0.708; n = 30) vs. placebo (n = 28). Drug-related adverse events were experienced by 2%, 8%, and 5% of patients in the placebo, benralizumab Q4W, and benralizumab Q8W arms. CONCLUSIONS: Benralizumab reduced annual asthma exacerbation rates, increased lung function, and was well-tolerated by Korean patients with severe, uncontrolled eosinophilic asthma.

Higher Binding Affinity and In Vitro Potency of Reslizumab for Interleukin-5 Compared With Mepolizumab

Reslizumab and mepolizumab are recently approved monoclonal antibodies for the treatment of severe (uncontrolled) eosinophilic asthma. Both are effective in neutralizing the function of interleukin-5 (IL-5). This study is the first to compare the binding affinity and in vitro potency of both antibodies in head-to-head assays. Two assays assessed binding affinity (using the equilibrium dissociation constant [K(D)]) of each drug for human IL-5. In the Biacore surface plasmon resonance assay, the association constant (k(on)) values for human IL-5 for reslizumab and mepolizumab were 3.93 × 10⁶ and 1.83 × 10⁵, respectively. The dissociation constant (k(off)) values were 4.29 × 10⁻⁴ and 2.14 × 10⁻⁴, respectively. Calculated K(D) values for human IL-5 for reslizumab and mepolizumab were 109 and 1,170 pM, respectively, representing an approximately 11-fold stronger binding affinity with reslizumab. In the Kinetic Exclusion Assay, the k(on) values for human IL-5 for reslizumab and mepolizumab were 3.17 × 10⁶ and 1.32 × 10⁵, respectively. The k(off) values were 1.36 × 10⁻⁵ and 1.48 × 10⁻⁵, respectively. Measured K(D) values for human IL-5 for reslizumab and mepolizumab were 4.3 and 112 pM, respectively, representing an approximately 26-fold stronger binding affinity for reslizumab. A human-IL-5-dependent cell proliferation assay was developed to assess in vitro potency, based on a human cell line selected for enhanced surface expression of IL-5 receptor-alpha and consistent proliferation response to IL-5. The concentration at which 50% inhibition occurred (IC₅₀) was determined for both antibodies. Reslizumab and mepolizumab inhibited IL-5-dependent cell proliferation, with IC₅₀ values of approximately 91.1 and 286.5 pM, respectively, representing on average 3.1-fold higher potency with reslizumab. In conclusion, comparative assays show that reslizumab has higher affinity binding for and in vitro potency against human IL-5 compared with mepolizumab. However, these results do not take into consideration the different methods of administration of reslizumab and mepolizumab.

The protective effect of interleukin-5 in septic mice / 中华内科杂志

To investigate the protective effect of interleukin-5 (IL-5) in septic mice,male C57BL/6 mice were divided into three groups including sepsis group with intraperitoneal injection of lipopolysaccharide (LPS,20 mg/kg),study group with combined IL-5 (1 μg per mouse) and LPS (20 mg/kg),control group with normal saline.Pathological changes were tested including lung,heart and kidney tissues.The serum cardiac troponin I (cTnI),serum creatinine (SCr),blood urea nitrogen (BUN),tumor necrosis factor α (TNFα),IL-6,IL-1β,and the chemokine (C-X-C motif) ligand 1(CXCL1) were measured and the survival at 7 d after treatment were recorded.Compared with sepsis group,tissue damages of lung,heart and kidney in IL-5 intervention group were ameliorated.The cTnI,SCr,BUN levels in study group were significantly decreased at 24 h (P＜0.05).In addition,TNFα was significantly decreased at 3 h (P＜0.05),and CXCL1 decreased at 12 h (P＜0.05),while IL-6 and IL-1β were similar at each time point (P＞0.05).The mortality at 7 d was less in IL-5 treatment group.In summary,IL-5 has a protective effect and reduces the inflammatory response in septic mice.

Efficacy and safety of benralizumab in patients with eosinophilic asthma: a meta-analysis of randomized placebo-controlled trials / 医学前沿

Benralizumab is a monoclonal antibody that targets interleukin-5 receptor α to deplete blood eosinophils and improve the clinical outcomes of allergic asthma. We conducted a meta-analysis to evaluate the safety and efficacy of different doses of benralizumab in patients with eosinophilic asthma. All randomized controlled trials involving benralizumab treatment for patients with eosinophilic asthma, which were searched in PubMed, Embase, and the Cochrane Library published until January 2017, as well as the rate of asthmatic exacerbation, pulmonary functionality, asthma control, quality of life scores, and adverse events were included. Randomized-effect models were used in the meta-analysis to calculate the pooled mean difference, relative risks, and 95% confidence intervals. Five studies involving 1951 patients were identified. Compared with the placebo, benralizumab treatment demonstrated significant improvements in the forced expiratory volume in 1 s (FEV1), Asthma Quality of Life Questionnaire scores, decreased asthmatic exacerbation and Asthma Control Questionnaire-6 (ACQ-6) scores. Benralizumab treatment was also not associated with increased adverse events. These findings indicated that benralizumab can be safely used to improve FEV1, enhance patient symptom control and quality of life, and reduce the risk of exacerbations and ACQ-6 scores in patients with eosinophilic asthma. Furthermore, our meta-analysis showed that benralizumab with 30 mg (every eight weeks) dosage can improve the health-related quality of life and appear to be more effective than 30 mg (every four weeks) dosage. Overall, data indicated that the optimal dosing regimen for benralizumab was possibly 30 mg (every eight weeks).

The effect of Qushi-Huaban granule for allergic purpura / 国际中医中药杂志

Objective To explore the effect of Qushi-Huaban granule for the allergic purpura and the impact on CD4+CD25+T cells. Methods A total of 80 children with allergic purpura from March 2014 to January 2016 were randomly divided into two groups, the control group and observation group, 40 in each group. The control group was given routine medicine andmontelukast chewable tablets. The observation group was treated with Qushi-Huaban granule on the basis of conventional therapy. The clinical effect, purpura recession time, recurrence rate before and after treatment were observed and compared. The serum levels of IFN-γ (interferon-γ, IFN-γ) and IL-5 were detected by ELISA. The expression level of CD4+CD25+ Treg were observed by flow cytometry before and after treatment. Results The effective rate of the treatment group [92.5% (37/40) vs. 72.5%(29/40), χ2=9.270] was significantly higher than control group (P＜0.01). After treatment, the serum IFN-γ levels in the observation group and the control group were significantly higher than those before treatment (t=3.960, 4.175, P＜0.05). The serum IL-5 levels of two groups were significantly lower than those before treatment (t=8.061, 8.776, P＜0.01).There was no significant differencein the serum INF-γ and IL-5 leves after treatment between two groups (P＞0.05). The regression time of purpura in the observation group (5.2 ± 1.1 d vs. 10.2 ± 2.4 d, t=12.460) was significantly shorter than that in the control group ( P＜0.01). The recurrence rate of the observation group was [7.4% (5/37) vs. 10.3% (3/29)] which was significantly lower than that of the control group, but the difference was not statistically significant (χ2=0.153, P=0.696). The CD4+CD25+T cells (t=7.367, 6.957, P＜0.05) and CD3+CD4+CD25+ T cells (t values were 9.080, 8.885, P＜0.05) of two groupswere significantly higher than those beforetreatment, butthere was no significant difference between the 2 groups after treatment ( P＞0.05). Conclusions The Qushi-Huaban granule combined with montelukast sodium for Henoch Schonlein purpura showed efficacy, and significantly increase the moisture level of T cell subsets.

Add-on Therapy for Symptomatic Asthma despite Long-Acting Beta-Agonists/Inhaled Corticosteroid / 결핵

Asthma, remains symptomatic despite ongoing treatment with high doses of inhaled corticosteroids (ICS) in conjunction with long-acting beta-agonists (LABA), is classified as “severe” asthma. In the course of caring for those patients diagnosed with severe asthma, stepping up from ICS/LABA to more aggressive therapeutic measures would be justified, though several aspects have to be checked in advance (including inhaler technique, adherence to therapy, and possible associated comorbidities). That accomplished, it would be advisable to step up care in accordance with the Global Initiative for Asthma (GINA) recommendations. Possible strategies include the addition of a leukotriene receptor antagonist or tiotropium (to the treatment regimen). The latter has been shown to be effective in the management of several subgroups of asthma. Oral corticosteroids have commonly been used for the treatment of patients with severe asthma in the past; however, the use of oral corticosteroids is commonly associated with corticosteroid-related adverse events and comorbidities. Therefore, according to GINA 2017 these patients should be referred to experts who specialize in the treatment of severe asthma to check further therapeutic options including biologics before starting treatment with oral corticosteroids.

Terapia anti interleukina 5 para la rinosinusitis crónica con pólipos / Anti-interleukin 5 therapy for chronic rhinosinusitis with polyps

Resumen INTRODUCCIÓN: La rinosinusitis crónica es la inflamación de la mucosa nasosinusal de duración superior a 12 semanas. Se distinguen dos formas clínicas: rinosinusitis crónica con pólipos y sin pólipos. Los pacientes con rinosinusitis crónica con pólipos presentan niveles elevados de interleukina 5, la cual promueve la diferenciación y supervivencia de eosinófilos, por lo que se ha propuesto minimizar su circulación como una nueva estrategia de tratamiento. Sin embargo, no hay claridad respecto a su real efectividad. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos tres revisiones sistemáticas que en conjunto incluyeron tres estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que los inhibidores de interleukina 5 podrían disminuir el puntaje de pólipos nasales. Si bien podrían asociarse a efectos adversos, estos serían poco frecuentes y de baja severidad. Sin embargo, la certeza de la evidencia es baja.

Abstract INTRODUCTION: Chronic rhinosinusitis is the inflammation of sinonasal mucosa lasting longer than 12 weeks. Two clinical forms are distinguished: chronic rhinosinusitis with polyps and without polyps. Patients with chronic rhinosinusitis with polyps exhibit high levels of interleukin 5, which promotes differentiation and survival of eosinophils. So, minimizing their circulation has been proposed as a new treatment strategy. However, there is no clarity regarding its real effectiveness. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified three systematic reviews included three primary studies overall, all corresponding to randomized trials. We concluded inhibitors of interleukin 5 might decrease nasal polyps score. Although they might be associated with adverse effects, these would be infrequent and of low severity. However, the certainty of the evidence is low.

Episodic angioedema associated with eosinophilia

Abstract: We report a 12-year-old girl who presented with recurrent angioedema on the face, trunk, and extremities, and concomitant marked weight gain for 5 years. During the episode, her white blood cell count increased to 47.7×109/L with 89.9% eosinophils, followed by elevated serum level of IL-5, IgE, IgM, and LDH. Histopathology showed perivascular eosinophilic infiltration and diffuse eosinophilic infiltration throughout the dermis. Possible causes of hypereosinophilia and eosinophilic infiltration of vital organs were ruled out. We also tested the FIP1L1/PDGFRa and ETV6/PDGFRb fusion gene to exclude the possibility of myeloid and lymphatic vessel neoplasms. The patient was treated with methylprednisolone and discharged with an oral prednisolone taper, which resulted in complete remission of the edema and normalization of peripheral blood eosinophil count, serum IL-5 level, IgE, IgM, and LDH.

Acupoint therapy can reduce airway inflammation and control asthma symptoms / 中华物理医学与康复杂志

Objective To investigate the effects of acupoint therapy on inflammatory factors and its clini-cal efficacy in relieving bronchial asthma. Methods Selected patients with bronchial asthma which was in remis-sion were randomly divided into a treatment group that was treated with acupoint therapy and a control group that was given Seretide. Each group had 30 cases. The treatment period was 4 weeks. Both groups were evaluated in terms of Asthma Control Test ( ACT) scores and the serum content of interleukin-5 ( IL-5) and interleukin-10 ( IL-10) before and at one month ( short-term) , as well as three months after the end of the treatment ( long-term) . The asthma control situation ( fully controlled, partially controlled or uncontrolled) was evaluated. Results Before treatment the average ACT scores of the two groups were not significantly different. After the treatment both the short-term and long-term average ACT scores of the treatment group were significantly higher than those of the con-trol group. The total effectiveness rate of asthma control in the treatment group in the short term ( 93%) was signifi-cantly higher than that in the control group ( 70%) . After the treatment the IL-5 and IL-10 levels in the treatment group were improved to a significantly greater extent than those in the control group. Conclusion Acupoint thera-py can reduce airway inflammation, control bronchial asthma symptoms and show good clinical efficacy, probably by regulating IL-5 and IL-10 levels.

Interleukin-10 and interleukin-5 balance in patients with active asthma, those in remission, and healthy controls

BACKGROUND: The immunological mechanisms of asthma remission remain unclear although several reports have suggested that balance between T helper (Th) 2 cytokines and regulatory cytokines is related. OBJECTIVE: To study the balance between interleukin (IL) 10 and IL-5 in asthma clinical remission. METHODS: We measured the numbers of IL-5 and IL-10 producing cells in peripheral blood mononuclear cells stimulated with mite antigen obtained from patients with active asthma (group A, n = 18), patients in clinical remission (group R, n = 15) and nonatopic healthy controls (group H, n = 14). RESULTS: The numbers of IL-5 producing cells in groups A and R were significantly higher than in group H. The number of IL-5 producing cells was lower in group R than in group A, although the difference was not statistically significant. The number of IL-10 producing cells was higher in group R than in group A, although again the difference was not statistically significant. There was a significant difference in the number of IL-10 producing cells between groups A and H but not between groups R and H. The ratio of the number of IL-10 to IL-5 producing cells was highest in group H followed by groups R and A, and the differences were statistically significant for each pair of groups. CONCLUSION: Our study suggests that the IL-10/IL-5 balance is related to clinical asthma. The balance differs between patients in clinical remission and healthy controls, suggesting that allergic inflammation may continue even after clinical asthma remission.

Sesamin attenuates inflammation response in a murine model of asthma / 中国药理学通报

Aim To investigate the effects of sesamin on inflammation response of asthma and to explore its possible mechanism of action. Methods Forty male BALB/c mice were randomly divided into five groups with 8 mice in each group: normal group, ovalbumin ( OVA) group, sesamin low dose group, sesamin high dose group and dexamethasone( DXM) group. Asthma model mice were induced by OVA in vivo. The left lung was isolated for pathological examination. Experi-ment of ELISA and Western blot were used to deter-mine the effect of sesamin on IL-4 , IL-5 , IL-13 and IFN-γ expression. Hematoxylin and eosin stain was used to investigate pathological examination in lung tis-sue. Western blot was performed to detect the IκBαphosphorylation and NF-κB nuclear translocation. Re-sults The mice developed the following pathophysio-logical features of asthma: increased numbers of in-flammatory cells, increased levels of IL-4, IL-5 and IL-13 , decreased level of IFN-γ in bronchoalveolar lavage fluids ( BALF ) and lung tissues ( P <0. 05 ) , and increased IκBα phosphorylation and NF-κB nucle-ar translocation in lung tissues ( P <0. 05 ) . Adminis-tration of sesamin markedly reduced airway inflammato-ry cell recruitment, reduced the production of IL-4, IL-5 , IL-13 and increased IFN-γ in BALF and lung tissues( P <0. 05 ) . The increased IκBα phosphoryla-tion and NF-κB nuclear translocation after OVA inhala-tion were inhibited by the administration of sesamin. Conclusion Sesamin attenuates inflammation re-sponse of asthma through suppression of NF-κB activa-tion.

Expressions of interleukin-4,5 and 13 in ocular surface with different types of allergic conjunctivitis / 中华实验眼科杂志

Background The pathogenesis of allergic conjunctivitis has not been clearly established.Current researchers indicate that interleukin-4 (IL-4), IL-5 and IL-13 may play an important role in allergic conjunctivitis.But whether the roles of these inflammatory factors are same in different types of allergic conjunctivitis remains unclear.Objective This study was to investigate the expressions of IL-4, IL-5 and IL-13 in ocular surface with different types of allergic conjunctivitis.Methods A prospective cohort study was designed.Eighty individuals were recruited in Shanxi Eye Hospital from April 2013 to September 2014, including 20 patients with vernal keratoconjunctivitis (VKC), 20 patients with seasonal allergic conjunctivitis (SAC), 20 patients with perennial allergic conjunctivitis (PAC) and 20 normal healthy subjects.Surficial tissues were binocularly scraped using disinfected scraper from upper eyelid conjunctiva, and 4 μl of tear fluid was obtained with capillary tube.The expressions of IL-4, IL-5 and IL-13 protein and mRNA in the conjunctival epithelial cells were detected by immunohistochemistry and real-time fluorescence quantitative PCR.The IL-4, IL-5 and IL-13 concentrations in tear fluid were assayed by Luminex method.This study complied with Declaration of Helsinki and the research protocol was approved by the Shanxi Eye Hospital Ethics Committee.Written informed consent was obtained from each subject prior to entering the cohort.Results IL-4, IL-5 and IL-13 were positively expressed in cytoplasm of conjunctival epithelial cells in the VKC group,SAC group and PAC group,but the expressions of IL-4,IL-5 and IL-13 were absent in the normal control group.The relative expression levels of IL-4 mRNA were 4.11±1.24,2.71±0.71 and 2.00±0.80;the relative expression levels of IL-5 mRNA were 4.02±0.43,2.07±0.45 and 1.47±0.50;and the relative expression levels of IL-13 mRNA expression levels were 6.44±0.66,4.35±1.26 and 2.39±0.86 in the VKC group,SAC group and PAC group, showing significant differences among the 4 groups (F =51.32,220.18,162.49, all at P＜0.01).The relative expression levels of IL-4,IL-5 and IL-13 mRNA were significantly higher in the VKC group than those in the SAC group and PAC group;and those in the SAC group were significantly elevated in comparison with the PAC group (all at P＜0.05).No IL-4, IL-5 and IL-13 were detected in the tear fluid in the normal control group;while the concentrations of IL-4,IL-5 and IL-13 in the tear fluid were (14.06±3.50), (10.88±1.82) and (34.28±8.42) pg/ml in the VKC group,and (7.71 ±0.65), (5.10± 1.33), (23.77±6.29) pg/ml in the SAC group as well as (3.30± 1.50) pg/ml, (2.43± 1.28) pg/ml and (17.67 ± 4.28) pg/ml in the PAC group, showing significant differences among the 3 groups (F =200.29,260.49,128.23, all at P＜0.01).IL-4, IL-5 and IL-13 concentrations in the tear fluid were significantly higher in the VKC group than those in the SAC group and PAC group,and those in the SAC group were significantly raised in comparison with the PAC group (all at P＜0.01).Conclusions IL-4,IL-5 and IL-13 participate in the pathogenesis of multiple allergic conjunctivitis,but their expressions in the ocular surficial tissue are discriminatory in different types of allergic conjunctivitis.

Effects of lactobacillus on the histamine,IL-5,IL-12 in serum and ICAM-1 in tissue of the allergic rhinitis rat model / 重庆医学

Objective To study the effect of lactobacillus on serum histamine ,interleukin‐5(IL‐5) ,interleukin‐12(IL‐12) and tissue intercellular cell adhesion molecule‐1(ICAM‐1) on the rats of allergic rhinitis model .Methods Totally 48 male SD rats were randomly divided into control group ,model group ,Lactobacillus (LBA) group (1 × 1010 CUF/kg) and loratadine (LRD) group (5 mg/kg) ,there were 12 SD rats in each group .LBA Group administered once daily for a total of 6 weeks ;LRD group administered once daily for seven days .Then the clinical symptoms indexes ,the content of serum histamine ,IL‐5 ,IL‐12 ,the changes of tissue pathological ,the mRNA and protein of ICAM‐1 were compared .Results Lactobacilli can significantly improve symptoms score of allergic rhinitis in rats ,the pathological score ,reduce serum histamine ,IL‐5 levels ,ICAM‐1 mRNA and protein expression of tissue , and increase IL‐12 proportion ,thus it showed significant efficacy .Conclusion Long‐term (approximately six weeks) given lactoba‐cilli played a therapeutic role of allergic rhinitis by reducing serum histamine ,IL‐5 levels and ICM A‐1 expression in tissues ,in‐creased serum IL‐12 level .

Serial Changes in Serum Eosinophil-associated Mediators between Atopic and Non-atopic Children after Mycoplasma pneumoniae pneumonia

PURPOSE: Mycoplasma pneumoniae pneumonia (MP) is associated with the exacerbation, timing, and onset of asthma. The goal of this study was to elucidate the impact of MP on eosinophil-related hyper-reactive amplification in atopic children. METHODS: We studied 48 patients with MP (26 atopic, 22 non-atopic), between 3 and 12 years of age. Serial changes in blood eosinophil counts, serum interleukin-5 (IL-5), and serum eosinophil cationic protein (ECP) levels were measured in atopic and non-atopic children with MP upon admission, recovery, and at 2 months post-recovery. Serum IL-5 and ECP levels were measured by enzyme-linked immunosorbent assays; eosinophil counts were measured using an autoanalyzer. RESULTS: Serial changes in serum IL-5, ECP, and total eosinophil counts were significantly higher in atopic patients, relative to non-atopic controls (P< or =0.001). Serum IL-5 and ECP levels were significantly higher in atopic patients at all three time points tested, while eosinophil counts were higher in the clinical recovery and follow-up phases, but not in the acute phase. Furthermore, among atopic patients, serum ECP levels were significantly higher in the recovery and follow-up phases than in the acute phase. CONCLUSIONS: The present study demonstrated significant differences in eosinophil counts, serum IL-5, and serum ECP levels between atopic and non-atopic children with MP at admission, recovery, and 2 months after clinical recovery. These outcomes are suggestive of eosinophil-related hyperreactivity in atopic children, with this status maintained for at least 2 months after MP.

Clinical significance of IgE and IL-5 in diagnosis of mycoplasma pneumoniae children with bronchial asthma / 中国基层医药

Objective To explore the clinical value of IgE and IL-5 in diagnosis of mycoplasma pneumoniae children with bronchial asthma.Methods 40 mycoplasma pneumoniae infection children complicated with bronchial asthma were chosen as the observation group,the other 40 mycoplasma pneumoniae infection children without bronchial asthma were selected as the control group.All children were admitted to hospital,the next morning fasting blood was obtained to detect IgE and IL-5 levels.Results The serum total IgE level of observation group was (335.74 ±38.84) IU/ml,the level of IL-5 was (311.86 ± 35.28) ng/L,which were significantly higher than control group (P ＜0.05).Binary Logistic regression analysis showed that,serum IgE level and IL-5 level had statistically significant difference (P ＜ 0.05).Conclusion Mycoplasma pneumoniae infection in children with bronchial asthma,the IgE and IL-5 levels increased more obviously,and the levels of serum IgE and IL-5 were important risk factors of onset of children with Mycoplasma pneumoniae infection combined bronchial asthma.

Hypereosinophilia-associated Diseases and the Therapeutic Agents in Development / 한양의대학술지

Eosinophil is one of the most enigmatic leukocytes that plays pleiotropic roles in initiation and propagation of inflammatory conditions, modulation of innate and adaptive immune responses, homeostasis, and remodeling and repair of diverse tissues in health and disease. Eosinophils arise from CD34+ hematopoietic cells in the bone marrow under the influence of transcription factors (C/EBPalpha and GATA-1) and hematopoietic cytokines (IL-5, IL-3, and GM-CSF). The unusually high numbers of eosinophils in blood and/or tissues, so-called hypereosinophilia, are often critically involved in pathophysiology of a wide variety of inflammatory diseases in many organs, including many allergic diseases (asthma, rhinitis, conjunctivitis, atopic dermatitis), gastrointestinal diseases (eosinophilic eosophagitis, ulcerative colitis, Crohn's disease, Duchenne's muscular dystrophy, idiopathic myositis), cancers (pancreas, bladder, liver, kidney, breast, melanoma, colon, glioblastoma, gastric, uterine, oral/nasal, lung), infectious diseases (helminth, bacteria, virus, fungi), transplantation rejection (lung, cardiac, corneal, skin, liver, and renal), reproduction, and autoimmune diseases. A dozen of therapeutic agents, notably including humanized anti-IL-5 monoclonal antibodies, that directly and indirectly target eosinophils have been developed and are studied extensively under clinical and preclinical trials. Some agents have been shown to have promising perspectives to hypereosinophilic diseases, especially against asthma exacerbations and hypereosinophilic syndromes. Further studies are required for discovery of the specific mechanisms of actions of the different eosinophil-targeted therapies, dosing strategies and treatment options with identification of biomarkers that can monitor and predict the responses.

Mycoplasma pneumoniae Infection Affects the Serum Levels of Vascular Endothelial Growth Factor and Interleukin-5 in Atopic Children

PURPOSE: Previous studies have outlined mechanisms by which Mycoplasma pneumonia (M. pneumonia) infection may promote allergic lung inflammation and airway remodeling, and increasing evidence from human studies suggests that atypical bacterial infections contribute to asthma exacerbation, chronic asthma, and disease severity with changes in cytokine expression. The present study evaluated changes in serum levels of vascular endothelial growth factor (VEGF) and interleukin (IL)-5 in atopic children with Mycoplasma pneumoniae pneumonia. METHODS: We recruited a total of 72 children with pneumonia. The patients were divided into 4 groups: atopic children with M. pneumonia pneumonia (group I, n=24), non-atopic children with M. pneumonia pneumonia (group II, n=23), atopic children with viral pneumonia (group III, n=13), and non-atopic children with viral pneumonia (group IV, n=12). Serum levels of IL-5, IL-13, VEGF, and tumor necrosis factor-alpha were measured at admission and at recovery using enzyme-linked immunosorbent assays. RESULTS: Serum levels of VEGF and IL-5 were elevated in group I compared with the other groups at both admission phase and clinical recovery phase. In group I, serum levels of VEGF and IL-5 were higher at recovery phase than at admission phase (VEGF: 1,102.2+/-569.4 vs. 874.9+/-589.9 pg/mL, respectively; IL-5: 150.5+/-63.9 vs. 120.2+/-46.7 pg/mL, respectively). CONCLUSIONS: The serum levels of VEGF and IL-5 were more increased in atopic children with M. pneumonia pneumonia than in the other groups. In this group, the serum levels of VEGF and IL-5 were more increased at recovery phase than at admission phase. The results of this study suggest that increases in VEGF and IL-5 may contribute to the development of hypersensitivity during M. pneumonia infection. These cytokines may act through their respective pro-inflammatory pathways to aggravate the allergic status and induce airway hypersensitivity during M. pneumonia pneumonia in atopic children.