Anti‐interleukin‐13 and anti‐interleukin‐4 agents versus placebo, anti‐interleukin‐5 or anti‐immunoglobulin‐E agents, for people with asthma

2021 ◽  
Author(s):  
Andrew Gallagher ◽  
Michaela Edwards ◽  
Parameswaran Nair ◽  
Stewart Drew ◽  
Aashish Vyas ◽  
...  
Keyword(s):  
Immunoglobulin E ◽  
Interleukin 4 ◽  
Interleukin 5 ◽  
Interleukin 13

Effect of Theaflavin on Inflammatory and Remolding of Airway in the Asthma Mice

2021 ◽  
Vol 11 (6) ◽  
pp. 1091-1098
Author(s):  
Jingju Hu ◽  
Jing Yang ◽  
Hua Guo ◽  
Xuesong Yao ◽  
Haiyan Qiu ◽  
...  
Keyword(s):  
Interleukin 4 ◽  
Control Group ◽  
Model Group ◽  
Interleukin 5 ◽  
Treatment Groups ◽  
Interleukin 13 ◽  
Asthma Model ◽  
Lung Resistance ◽  
Neutrophile Granulocytes ◽  
Number Of Cells

To study the effect of theaflavin on the airway’s inflammation and remodeling in mice with asthma. The mice were divided into the control, asthma model, and the theaflavin treatment groups to analyze the changes in pulmonary compliance and lung resistance of the mice with asthma to theaflavin treatment. The theaflavin treatment groups consisted of the low-dose (15 mg/kg theaflavin-intragastric administration), medium-dose (30 mg/kg), and high-dose (60 mg/kg) groups. Alveoli lavage liquid was gathered from the mice to count the number of inflammatory cells, and the levels of interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13), and eotaxin were detected by ELISA. The levels of proteins, such as transforming growth factor-1 (TGF-1), alpha-smooth muscle actin (α-SMA), CyclinD1,CyclinD2, Toll-like receptors-4 (TLR4), myeloid differentiation factor 88 (MyD88), and NF-κBp65, which showed the performance of lung tissue was tested by Western blotting. Compared to the control group, the lung resistance of the asthma model mice was increased, and compliance was decreased after increasing concentrations of acetylcholine (Mch) stimulation. Compared to the asthma model group, the pulmonary resistance was decreased, and pulmonar compliance was increased according to the rising concentration of Mch in theaflavin-L, theaflavin-M and theaflavin-H mice. Compared to the control group, the number of cells, macrophages, acidophilic cells, lymph, and neutrophile granulocytes increased in the alveolar perfusion fluid of asthmatic mice. The level of interleukin 4, interleukin 5, interleukin 13, and eotaxin, TGF-β1, α-SMA, Cyclin D1, MyD88, TLR4, Cyclin D2, and NF-κBp65 proteins of the lung was also increased. Compared to the model group, the number of cells, macrophages, acidophilic cells, lymph, and neutrophile granulocytes were decreased successively in the alveolar lavage fluid in the theaflavin-L, theaflavin-M, and theaflavin-H mice. Meanwhile, the content of interleukin 4, interleukin 5, interleukin 13, and eotaxin were decreased successively, and the level of TGF-β1, α-SMA, Cyclin D1, MyD88, TLR4, Cyclin D2, and NF-Bp65 protein increased successively in the theaflavin-L, theaflavin-M, and theaflavin-H mice. Theaflavin has been found to reduce airway inflammation, impede airway remodeling, and decrease the TLR 4/MyD88/NF-B signaling in asthmatic mice.

Monoclonal Antibody Therapy in Sinonasal Disease

2017 ◽  
Vol 31 (2) ◽  
pp. 93-95 ◽  
Author(s):  
Sergio E. Chiarella ◽  
Hendrik Sy ◽  
Anju T. Peters
Keyword(s):  
Nasal Polyps ◽  
Immunoglobulin E ◽  
Antibody Therapy ◽  
Standard Of Care ◽  
Biologic Agents ◽  
Interleukin 4 ◽  
Monoclonal Antibody Therapy ◽  
Interleukin 5 ◽  
Sinonasal Disease ◽  
The U.S

Chronic rhinosinusitis (CRS) affects 12.5% of the U.S. population. CRS can be divided into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps. Some individuals with CRSwNP do not respond to standard-of-care medical and surgical management. For these individuals, targeted biologic agents are emerging as an important therapeutic alternative. In this review, we described the most-relevant studies that addressed the use of anti-immunoglobulin E (omalizumab), anti-interleukin 5 (mepolizumab and reslizumab), and anti-interleukin 4/interleukin 13 (dupilumab) monoclonal antibodies for the treatment of CRSwNP. In addition, we discussed the importance of some of these clinical trials in identifying new CRS endotypes based on distinct inflammatory profiles.

Interleukin 4 and the Related Cytokines (Interleukin 5 and Interleukin 13)

2016 ◽  
pp. 678-686
Author(s):  
Chrysanthi Skevaki ◽  
Christoph Hudemann ◽  
Harald Renz
Keyword(s):  
Interleukin 4 ◽  
Interleukin 5 ◽  
Interleukin 13

Interleukin-4/interleukin-13 versus interleukin-5

2019 ◽  
Vol 19 (1) ◽  
pp. 30-37 ◽  
Author(s):  
Albert Y. Wu ◽  
Sanjiv Sur ◽  
J. Andrew Grant ◽  
Julia W. Tripple
Keyword(s):  
Interleukin 4 ◽  
Interleukin 5 ◽  
Interleukin 13

scholarly journals Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity.

1996 ◽  
Vol 183 (1) ◽  
pp. 109-117 ◽  
Author(s):  
D B Corry ◽  
H G Folkesson ◽  
M L Warnock ◽  
D J Erle ◽  
M A Matthay ◽  
...  
Keyword(s):  
Murine Model ◽  
Immunoglobulin E ◽  
Lavage Fluid ◽  
Airway Hyperreactivity ◽  
Interleukin 4 ◽  
Immunodeficient Mice ◽  
Interleukin 5 ◽  
Th2 Cytokine ◽  
Subsequent Response ◽  
Airway Responses

Reversible airway hyperreactivity underlies the pathophysiology of asthma, yet the precise mediators of the response remain unclear. Human studies have correlated aberrant activation of T helper (Th) 2-like effector systems in the airways with disease. A murine model of airway hyperreactivity in response to acetylcholine was established using mice immunized with ovalbumin and challenged with aerosolized antigen. No airway hyperractivity occurred in severe combined immunodeficient mice. Identically immunized BALB/c mice developed an influx of cells, with a predominance of eosinophils and CD4+ T cells, into the lungs and bronchoalveolar lavage fluid at the time that substantial changes in airway pressure and resistance were quantitated. Challenged animals developed marked increases in Th2 cytokine production, eosinophil influx, and serum immunoglobulin E levels. Neutralization of interleukin (IL) 4 using monoclonal antibodies administered during the period of systemic immunization abrogated airway hyperractivity but had little effect on the influx of eosinophils. Administration of anti-IL-4 only during the period of the aerosol challenge did not affect the subsequent response to acetylcholine. Finally, administration of anti-IL-5 antibodies at levels that suppressed eosinophils to < 1% of recruited cells had no effect on the subsequent airway responses. BALB/c mice had significantly greater airway responses than C57BL/6 mice, consistent with enhanced IL-4 responses to antigen in BALB/c mice. Taken together, these data implicate IL-4 generated during the period of lymphocyte priming with antigen in establishing the cascade of responses required to generate airway hyperractivity to inhaled antigen. No role for IL-5 or eosinophils could be demonstrated.

scholarly journals Chemotherapy for Schistosomiasis in Ugandan Fishermen: Treatment Can Cause a Rapid Increase in Interleukin-5 Levels in Plasma but Decreased Levels of Eosinophilia and Worm-Specific Immunoglobulin E

2004 ◽  
Vol 72 (7) ◽  
pp. 4023-4030 ◽  
Author(s):  
Colin M. Fitzsimmons ◽  
Sarah Joseph ◽  
Frances M. Jones ◽  
Claus M. Reimert ◽  
Karl F. Hoffmann ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Immunoglobulin E ◽  
Transforming Growth Factor Β ◽  
Specific Ige ◽  
Blood Cultures ◽  
Interleukin 4 ◽  
Immune Reactions ◽  
Interleukin 5 ◽  
Specific Immunoglobulin E ◽  
Specific Immunoglobulin

ABSTRACT Chemotherapy for blood-dwelling schistosomes kills the worms and exposes parasite antigen to the circulation. In many people from areas of endemicity, this treatment increases parasite-specific immunoglobulin E (IgE) and other Th2 responses in the months following therapy, responses that have been associated with subsequent resistance to reinfection. Here we investigate much earlier changes in immune reactions after praziquantel therapy in Schistosoma mansoni-infected fishermen working in an area of high transmission in Uganda. The subjects gave blood before treatment and at 1 and 21 days posttreatment. Blood cultures were incubated with schistosome soluble worm antigen (SWA) or soluble egg antigen (SEA). Interleukin-4 (IL-4), IL-5, IL-10, IL-13, gamma interferon, and transforming growth factor β levels were measured in the cultures and in plasma. A marked transient increase in plasma IL-5 levels was observed in 75% of the subjects (n = 48) by 1 day posttreatment. This response was dependent on pretreatment intensity of infection and was accompanied by a transient decrease in eosinophil numbers. One day posttreatment, blood cultures from the 16 subjects with the greatest increase in plasma IL-5 level (>100 pg/ml) displayed reduced IL-5, IL-13, and IL-10 responses to SWA, and in contrast to the rest of the cohort, these high-IL-5 subjects displayed reduced levels of SWA-specific IgE in plasma 21 days posttreatment. Twenty months after treatment, the intensity of reinfection was positively correlated with the increase in plasma IL-5 level seen 1 day posttreatment. These studies describe the heterogeneity in early immune reactions to treatment, identifying subgroups who have different patterns of reaction and who may have different capacities to mount the responses that have been associated with resistance to reinfection.

scholarly journals Induction of Interleukin-4 and Interleukin-5 Expression in Mast Cells Is Inhibited by Glucocorticoids

1998 ◽  
Vol 5 (1) ◽  
pp. 18-23 ◽  
Author(s):  
William A. Sewell ◽  
Lyndee L. Scurr ◽  
Helen Orphanides ◽  
Simon Kinder ◽  
Russell I. Ludowyke
Keyword(s):  
Mast Cells ◽  
Phorbol Ester ◽  
Immunoglobulin E ◽  
Calcium Ionophore ◽  
Allergic Diseases ◽  
Interleukin 4 ◽  
Mrna Levels ◽  
Interleukin 5 ◽  
Highly Sensitive ◽  
In Cells

ABSTRACT Inflammation in asthma and other allergic diseases is characterized by excessive production of immunoglobulin E (IgE) and the influx of leukocytes, especially eosinophils. Interleukin 4 (IL-4) and IL-5 are essential for IgE production and eosinophilia, respectively, and are produced by mast cells in allergic conditions, for which glucocorticoids are widely used therapeutically. We assessed the effect of glucocorticoids on IL-4 and IL-5 mRNA production by the RBL-2H3 cell line, an analog of mucosal mast cells. IL-4 and IL-5 mRNAs were induced by an antigen that is used to cross-link receptor bound IgE, by calcium ionophore, or by ionophore with phorbol ester and were markedly inhibited by dexamethasone. In cells activated with ionophore and phorbol ester, 10−6 M dexamethasone reduced the IL-4 and IL-5 mRNA levels to only 12.8 and 5.7%, respectively, of those in cells without dexamethasone, and 10−9 M dexamethasone caused reductions to 27 and 56%, respectively. Hydrocortisone at 10−6 and 10−7 M almost completely inhibited IL-4 and IL-5 mRNA production. Dexamethasone was markedly inhibitory even if it was added after the cells were activated, provided that it was present in the cultures for at least 1.5 h. These studies indicate that the expression of IL-4 and IL-5 mRNAs by mast cells is highly sensitive to glucocorticoids. The data suggest that these inhibitory effects may contribute to the clinical efficacy of glucocorticoids in the therapy of allergic diseases.

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