{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T08:42:25Z","timestamp":1794300145860,"version":"4.9.0"},"reference-count":101,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Asthma is a\u00a0heterogeneous inflammatory disease characterized by airflow obstruction, wheezing, eosinophilia and neutrophilia of the airways. Identification of distinct inflammatory patterns characterizing asthma endotypes led to the development of novel therapeutic approaches. Cytokine or cytokine receptor targeting by therapeutic antibodies, such as anti-IL-4 and anti-IL-5, is now approved for severe asthma treatment. However, the complexity of cytokine networks in asthma should not be underestimated. Inhibition of one pro-inflammatory cytokine may lead to perturbed expression of another pro-inflammatory cytokine. Without understanding of the underlying mechanisms and defining the molecular predictors it may be difficult to control cytokine release that accompanies certain disease manifestations. Accumulating evidence suggests that in some cases a combined pharmacological inhibition of pathogenic cytokines, such as simultaneous blockade of IL-4 and IL-13 signaling, or blockade of upstream cytokines, such as TSLP, are more effective than single cytokine targeting. IL-6 and TNF are the important inflammatory mediators in the pathogenesis of asthma. Preliminary data suggests that combined pharmacological inhibition of TNF and IL-6 during asthma may be more efficient as compared to individual neutralization of these cytokines. Here we summarize recent findings in the field of anti-cytokine therapy of asthma and discuss immunological mechanisms by which simultaneous targeting of multiple cytokines as opposed to targeting of a single cytokine may improve disease outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2021.601842","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T04:25:37Z","timestamp":1621311937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Novel Anti-Cytokine Strategies for Prevention and Treatment of Respiratory Allergic Diseases"],"prefix":"10.3389","volume":"12","author":[{"given":"Ekaterina O.","family":"Gubernatorova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga A.","family":"Namakanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina. A.","family":"Gorshkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra D.","family":"Medvedovskaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei A.","family":"Nedospasov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina S.","family":"Drutskaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,18]]},"reference":[{"key":"B1","unstructured":"Global Strategy for Asthma Management and Prevention2020"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-018-8712-1","article-title":"Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease","volume":"56","author":"Kuruvilla","year":"2019","journal-title":"Clin Rev Allergy Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.2014.0847","article-title":"Severe Asthma: Definition, Diagnosis and Treatment","volume":"111","author":"Lommatzsch","year":"2014","journal-title":"Dtsch Arztebl Int"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00202013","article-title":"International ERS\/ATS Guidelines on Definition, Evaluation and Treatment of Severe Asthma","volume":"43","author":"Chung","year":"2014","journal-title":"Eur Respir J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.18176\/jiaci.0265","article-title":"Severe Asthma Phenotypes Classified by Site of Airway Involvement and Remodeling Via Chest CT Scan","volume":"28","author":"Kim","year":"2018","journal-title":"J Investig Allergol Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800709","article-title":"Bronchial Allergen Challenge of Patients With Atopic Asthma Triggers an Alarmin (IL-33, TSLP, and IL-25) Response in the Airways Epithelium and Submucosa","volume":"201","author":"Wang","year":"2018","journal-title":"J Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.imlet.2018.11.012","article-title":"Mouse Models of Severe Asthma for Evaluation of Therapeutic Cytokine Targeting","volume":"207","author":"Gubernatorova","year":"2019","journal-title":"Immunol Lett"},{"key":"B8","doi-asserted-by":"publisher","first-page":"301ra129","DOI":"10.1126\/scitranslmed.aab3142","article-title":"TH2 and TH17 Inflammatory Pathways are Reciprocally Regulated in Asthma","volume":"7","author":"Choy","year":"2015","journal-title":"Sci Trans Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4147","article-title":"An Asthma-Associated IL4R Variant Exacerbates Airway Inflammation by Promoting Conversion of Regulatory T Cells to TH17-like Cells","volume":"22","author":"Massoud","year":"2016","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00204.2020","article-title":"Therapeutic Efficacy of IL-17A Neutralization With Corticosteroid Treatment in a Model of Antigen-Driven Mixed-Granulocytic Asthma","volume":"319","author":"Menson","year":"2020","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901116","article-title":"Single and Synergistic Effects of Type 2 Cytokines on Eosinophils and Asthma Hallmarks","volume":"204","author":"Beckert","year":"2020","journal-title":"J Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1080\/02770903.2017.1283696","article-title":"Th-17 Regulatory Cytokines IL-21, IL-23, and IL-6 Enhance Neutrophil Production of IL-17 Cytokines During Asthma","volume":"54","author":"Halwani","year":"2017","journal-title":"J Asthma"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.06.032","article-title":"TGF-beta3 Promotes MUC5AC Hyper-Expression by Modulating Autophagy Pathway in Airway Epithelium","volume":"33","author":"Zhang","year":"2018","journal-title":"EBioMedicine"},{"key":"B14","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/1465-9921-14-118","article-title":"IL-22 Contributes to TGF-beta1-mediated Epithelial-Mesenchymal Transition in Asthmatic Bronchial Epithelial Cells","volume":"14","author":"Johnson","year":"2013","journal-title":"Respir Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00041.2012","article-title":"miR-140-3p Regulation of TNF-alpha-induced CD38 Expression in Human Airway Smooth Muscle Cells","volume":"303","author":"Jude","year":"2012","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.04.043","article-title":"SETD7 Promotes TNF-alpha-induced Proliferation and Migration of Airway Smooth Muscle Cells In Vitro Through Enhancing NF-kappaB\/CD38 Signaling","volume":"72","author":"Wu","year":"2019","journal-title":"Int Immunopharmacol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s12931-016-0462-0","article-title":"Impaired Anti-Inflammatory Action of Glucocorticoid in Neutrophil From Patients With Steroid-Resistant Asthma","volume":"17","author":"Wang","year":"2016","journal-title":"Respir Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124606","article-title":"Epithelial Cell-Derived Cytokines: More Than Just Signaling the Alarm","volume":"129","author":"Roan","year":"2019","journal-title":"J Clin Invest"},{"key":"B19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.immuni.2015.07.007","article-title":"Barrier Epithelial Cells and the Control of Type 2 Immunity","volume":"43","author":"Hammad","year":"2015","journal-title":"Immunity"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2000260","DOI":"10.1183\/13993003.00260-2020","article-title":"Anti-Alarmins in Asthma: Targeting the Airway Epithelium With Next-Generation Biologics","volume":"56","author":"Porsbjerg","year":"2020","journal-title":"Eur Respir J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4160","article-title":"GM-CSF Transgene Expression in the Airway Allows Aerosolized Ovalbumin to Induce Allergic Sensitization in Mice","volume":"102","author":"Stampfli","year":"1998","journal-title":"J Clin Invest"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/ni1247","article-title":"Thymic Stromal Lymphopoietin as a Key Initiator of Allergic Airway Inflammation in Mice","volume":"6","author":"Zhou","year":"2005","journal-title":"Nat Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"11721","DOI":"10.1038\/s41598-018-30259-2","article-title":"Chitin Promotes Antigen-Specific Th2 Cell-Mediated Murine Asthma Through Induction of IL-33-mediated IL-1beta Production by Dcs","volume":"8","author":"Arae","year":"2018","journal-title":"Sci Rep"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.04.051","article-title":"IL-25 Enhances Allergic Airway Inflammation by Amplifying a TH2 Cell-Dependent Pathway in Mice","volume":"118","author":"Tamachi","year":"2006","journal-title":"J Allergy Clin Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.06.008","article-title":"Anti-IL-33 Antibody Treatment Inhibits Airway Inflammation in a Murine Model of Allergic Asthma","volume":"386","author":"Liu","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3109\/02770903.2012.702841","article-title":"Beneficial Effect of Anti-interleukin-33 on the Murine Model of Allergic Inflammation of the Lower Airway","volume":"49","author":"Kim","year":"2012","journal-title":"J Asthma"},{"key":"B27","doi-asserted-by":"publisher","first-page":"66","DOI":"10.3109\/01902148.2013.870261","article-title":"Blockade of IL-33\/ST2 Ameliorates Airway Inflammation in a Murine Model of Allergic Asthma","volume":"40","author":"Lee","year":"2014","journal-title":"Exp Lung Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1016\/j.jaci.2019.08.039","article-title":"IL-33 Blockade Affects Mediators of Persistence and Exacerbation in a Model of Chronic Airway Inflammation","volume":"144","author":"Allinne","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.131347","article-title":"Phase 2a Randomized, Placebo-Controlled Study of anti-IL-33 in Peanut Allergy","volume":"4","author":"Chinthrajah","year":"2019","journal-title":"JCI Insight"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2174\/1874306401307010021","article-title":"Monoclonal Anti-TNF-alpha Antibodies for Severe Steroid-Dependent Asthma: A Case Series","volume":"7","author":"Taille","year":"2013","journal-title":"Open Respir Med J"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1016\/j.jaip.2019.02.043","article-title":"Treatment of Severe Persistent Asthma With IL-6 Receptor Blockade","volume":"7","author":"Esty","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e51268","DOI":"10.1371\/journal.pone.0051268","article-title":"Neutralization of TSLP Inhibits Airway Remodeling in a Murine Model of Allergic Asthma Induced by Chronic Exposure to House Dust Mite","volume":"8","author":"Chen","year":"2013","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1159\/000490865","article-title":"Thymic Stromal Lymphopoietin Signaling Pathway Inhibition Attenuates Airway Inflammation and Remodeling in Rats With Asthma","volume":"47","author":"Cheng","year":"2018","journal-title":"Cell Physiol Biochem"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-018-0239-x","article-title":"Anti-Thymic Stromal Lymphopoietin Antibody Suppresses Airway Remodeling in Asthma Through Reduction of MMP and CTGF","volume":"86","author":"Lin","year":"2019","journal-title":"Pediatr Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402895","article-title":"Effects of an Anti-TSLP Antibody on Allergen-Induced Asthmatic Responses","volume":"370","author":"Gauvreau","year":"2014","journal-title":"N Engl J Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1704064","article-title":"Tezepelumab in Adults With Uncontrolled Asthma","volume":"377","author":"Corren","year":"2017","journal-title":"N Engl J Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2019.10880","article-title":"Affinity Improvement of the Fully Human antiTSLP Recombinant Antibody","volume":"21","author":"Chen","year":"2020","journal-title":"Mol Med Rep"},{"key":"B38","doi-asserted-by":"crossref","DOI":"10.1164\/ajrccm-conference.2020.201.1_MeetingAbstracts.A4207","article-title":"Efficacy and Safety of an Inhaled Anti-TSLP Antibody Fragment in Adults With Mild Atopic Asthma","author":"Gauvreau","year":"2020"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.04.020","article-title":"Neonatal Rhinovirus Induces Mucous Metaplasia and Airways Hyperresponsiveness Through IL-25 and Type 2 Innate Lymphoid Cells","volume":"134","author":"Hong","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12558","article-title":"IL-25 in Allergic Inflammation","volume":"278","author":"Xu","year":"2017","journal-title":"Immunol Rev"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.07.051","article-title":"Blocking IL-25 Prevents Airway Hyperresponsiveness in Allergic Asthma","volume":"120","author":"Ballantyne","year":"2007","journal-title":"J Allergy Clin Immunol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1136\/thoraxjnl-2012-202003","article-title":"IL-25 Drives Remodelling in Allergic Airways Disease Induced by House Dust Mite","volume":"68","author":"Gregory","year":"2013","journal-title":"Thorax"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2018.248","article-title":"Blockade of Thymic Stromal Lymphopoietin and CRTH2 Attenuates Airway Inflammation in a Murine Model of Allergic Asthma","volume":"35","author":"Lee","year":"2020","journal-title":"Korean J Intern Med"},{"key":"B44","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.bbrc.2018.08.064","article-title":"Design and Characterization of Zweimab and Doppelmab, High Affinity Dual Antagonistic anti-TSLP\/IL13 Bispecific Antibodies","volume":"504","author":"Venkataramani","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12683","article-title":"The Interleukin-33 Receptor ST2 is Important for the Development of Peripheral Airway Hyperresponsiveness and Inflammation in a House Dust Mite Mouse Model of Asthma","volume":"46","author":"Zoltowska","year":"2016","journal-title":"Clin Exp Allergy"},{"key":"B46","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.jaci.2017.10.020","article-title":"Experimental Asthma Persists in IL-33 Receptor Knockout Mice Because of the Emergence of Thymic Stromal Lymphopoietin-Driven IL-9(+) and IL-13(+) Type 2 Innate Lymphoid Cell Subpopulations","volume":"142","author":"Verma","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1111\/all.13997","article-title":"Eosinophil Extracellular Traps Activate Type 2 Innate Lymphoid Cells Through Stimulating Airway Epithelium in Severe Asthma","volume":"75","author":"Choi","year":"2020","journal-title":"Allergy"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/resp.13711","article-title":"Combined Blockade of IL-25, IL-33 and TSLP Mediates Amplified Inhibition of Airway Inflammation and Remodelling in a Murine Model of Asthma","volume":"25","author":"An","year":"2020","journal-title":"Respirology"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1016\/j.jaci.2018.08.051","article-title":"IL-33 Drives Influenza-Induced Asthma Exacerbations by Halting Innate and Adaptive Antiviral Immunity","volume":"143","author":"Ravanetti","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s12931-019-1134-7","article-title":"Mepolizumab Reduces Exacerbations in Patients With Severe Eosinophilic Asthma, Irrespective of Body Weight\/Body Mass Index: Meta-Analysis of MENSA and MUSCA","volume":"20","author":"Albers","year":"2019","journal-title":"Respir Res"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2016.03.032","article-title":"Reslizumab for Inadequately Controlled Asthma With Elevated Blood Eosinophil Levels: A Randomized Phase 3 Study","volume":"150","author":"Bjermer","year":"2016","journal-title":"Chest"},{"key":"B52","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.anai.2019.10.006","article-title":"Benralizumab Efficacy for Patients With Fixed Airflow Obstruction and Severe, Uncontrolled Eosinophilic Asthma","volume":"124","author":"Chipps","year":"2020","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.13.1.7598937","article-title":"Interleukin-4 is Required for the Induction of Lung Th2 Mucosal Immunity","volume":"13","author":"Coyle","year":"1995","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5397.2258","article-title":"Interleukin-13: Central Mediator of Allergic Asthma","volume":"282","author":"Wills-Karp","year":"1998","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(18)30184-X","article-title":"Tralokinumab for Severe, Uncontrolled Asthma (STRATOS 1 and STRATOS 2): Two Randomised, Double-Blind, Placebo-Controlled, Phase 3 Clinical Trials","volume":"6","author":"Panettieri","year":"2018","journal-title":"Lancet Respir Med"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1800948","DOI":"10.1183\/13993003.00948-2018","article-title":"Tralokinumab did Not Demonstrate Oral Corticosteroid-Sparing Effects in Severe Asthma","volume":"53","author":"Busse","year":"2019","journal-title":"Eur Respir J"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)30265-X","article-title":"Efficacy and Safety of Lebrikizumab in Patients With Uncontrolled Asthma (LAVOLTA I and LAVOLTA II): Replicate, Phase 3, Randomised, Double-Blind, Placebo-Controlled Trials","volume":"4","author":"Hanania","year":"2016","journal-title":"Lancet Respir Med"},{"key":"B58","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.iac.2004.06.008","article-title":"Anti-Interleukin-4 Therapy","volume":"24","author":"Steinke","year":"2004","journal-title":"Immunol Allergy Clin North Am"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.4.6.743","article-title":"Use of Biologicals as Immunotherapy in Asthma and Related Diseases","volume":"4","author":"Walker","year":"2008","journal-title":"Expert Rev Clin Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-018-0702-4","article-title":"Liberty Asthma Quest: Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate Dupilumab Efficacy\/Safety in Patients With Uncontrolled, Moderate-to-Severe Asthma","volume":"35","author":"Busse","year":"2018","journal-title":"Adv Ther"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/all.13685","article-title":"Dupilumab Reduces Local Type 2 Pro-Inflammatory Biomarkers in Chronic Rhinosinusitis With Nasal Polyposis","volume":"74","author":"Jonstam","year":"2019","journal-title":"Allergy"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304048","article-title":"Dupilumab in Persistent Asthma With Elevated Eosinophil Levels","volume":"368","author":"Wenzel","year":"2013","journal-title":"N Engl J Med"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1042\/CS20050038","article-title":"TNF-alpha as a Promising Therapeutic Target in Chronic Asthma: A Lesson From Rheumatoid Arthritis","volume":"109","author":"Russo","year":"2005","journal-title":"Clin Sci (Lond)"},{"key":"B64","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/rr12","article-title":"Activation of Tumor Necrosis Factor Receptor 1 in Airway Smooth Muscle: A Potential Pathway That Modulates Bronchial Hyper-Responsiveness in Asthma","volume":"1","author":"Amrani","year":"2000","journal-title":"Respir Res"},{"key":"B65","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1111\/j.1365-2222.2006.02498.x","article-title":"Cysteinyl Leukotrienes: Multi-Functional Mediators in Allergic Rhinitis","volume":"36","author":"Peters-Golden","year":"2006","journal-title":"Clin Exp Allergy"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90890","article-title":"TNF is Required for TLR Ligand-Mediated But Not Protease-Mediated Allergic Airway Inflammation","volume":"127","author":"Whitehead","year":"2017","journal-title":"J Clin Invest"},{"key":"B67","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.154.10.5411","article-title":"TNF-Alpha Mediates Recruitment of Neutrophils and Eosinophils During Airway Inflammation","volume":"154","author":"Lukacs","year":"1995","journal-title":"J Immunol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0288OC","article-title":"Tumor Necrosis Factor-Alpha Induces Transforming Growth Factor-Beta1 Expression in Lung Fibroblasts Through the Extracellular Signal-Regulated Kinase Pathway","volume":"32","author":"Sullivan","year":"2005","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2005.02407.x","article-title":"Anti-Tumor Necrosis Factor-Alpha Antibody Treatment Reduces Pulmonary Inflammation and Methacholine Hyper-Responsiveness in a Murine Asthma Model Induced by House Dust","volume":"36","author":"Kim","year":"2006","journal-title":"Clin Exp Allergy"},{"key":"B70","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S1081-1206(10)60528-5","article-title":"Decrease in Airway Mucous Gene Expression Caused by Treatment With Anti-Tumor Necrosis Factor Alpha in a Murine Model of Allergic Asthma","volume":"103","author":"Busse","year":"2009","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200809-1512OC","article-title":"A Randomized, Double-Blind, Placebo-Controlled Study of Tumor Necrosis Factor-Alpha Blockade in Severe Persistent Asthma","volume":"179","author":"Wenzel","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011110","article-title":"Tuberculosis Associated With Infliximab, a Tumor Necrosis Factor Alpha-Neutralizing Agent","volume":"345","author":"Keane","year":"2001","journal-title":"N Engl J Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1002\/art.20311","article-title":"Lymphoma in Rheumatoid Arthritis: The Effect of Methotrexate and Anti-Tumor Necrosis Factor Therapy in 18,572 Patients","volume":"50","author":"Wolfe","year":"2004","journal-title":"Arthritis Rheum"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90001-2","article-title":"Tumor Necrosis Factor-Alpha is Required in the Protective Immune Response Against Mycobacterium Tuberculosis in Mice","volume":"2","author":"Flynn","year":"1995","journal-title":"Immunity"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.11.024","article-title":"TNF-alpha-induced Protein 3 (TNFAIP3)\/A20 Acts as a Master Switch in TNF-alpha Blockade-Driven IL-17A Expression","volume":"142","author":"Urbano","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1056\/NEJMoa050580","article-title":"Evidence of a Role of Tumor Necrosis Factor Alpha in Refractory Asthma","volume":"354","author":"Berry","year":"2006","journal-title":"N\u00a0Engl J Med"},{"key":"B77","doi-asserted-by":"publisher","first-page":"15025","DOI":"10.1038\/nrdp.2015.25","article-title":"Asthma","volume":"1","author":"Holgate","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200601-072OC","article-title":"The Effects of a Monoclonal Antibody Directed Against Tumor Necrosis Factor-alpha in Asthma","volume":"174","author":"Erin","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.10.3495.422k47_3495_3504","article-title":"Interleukin-6 and Soluble Interleukin-6 Receptor: Direct Stimulation of gp130 and Hematopoiesis","volume":"92","author":"Peters","year":"1998","journal-title":"Blood"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.4989","article-title":"IL-6 Trans-Signaling Via the Soluble IL-6 Receptor: Importance for the Pro-Inflammatory Activities of IL-6","volume":"8","author":"Rose-John","year":"2012","journal-title":"Int J Biol Sci"},{"key":"B81","doi-asserted-by":"publisher","first-page":"a028415","DOI":"10.1101\/cshperspect.a028415","article-title":"Interleukin-6 Family Cytokines","volume":"10","author":"Rose-John","year":"2018","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.07.004","article-title":"Interleukin-6: Biology, Signaling and Strategies of Blockade","volume":"26","author":"Schaper","year":"2015","journal-title":"Cytokine Growth Factor Rev"},{"key":"B83","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.coi.2015.02.008","article-title":"The IL-6\/gp130\/STAT3 Signaling Axis: Recent Advances Towards Specific Inhibition","volume":"34","author":"Garbers","year":"2015","journal-title":"Curr Opin Immunol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.clim.2008.08.018","article-title":"The Effects of IL-6 on CD4 T Cell Responses","volume":"130","author":"Dienz","year":"2009","journal-title":"Clin Immunol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.it.2009.09.009","article-title":"Suppressors of Cytokine Signaling (SOCS) in T Cell Differentiation, Maturation, and Function","volume":"30","author":"Palmer","year":"2009","journal-title":"Trends Immunol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.8.5186","article-title":"Aspergillus Fumigatus Generates an Enhanced Th2-biased Immune Response in Mice With Defective Cystic Fibrosis Transmembrane Conductance Regulator","volume":"177","author":"Allard","year":"2006","journal-title":"J Immunol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.151.5.7735584","article-title":"Circulating Interleukin-6 Levels in Patients With Bronchial Asthma","volume":"151","author":"Yokoyama","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)30048-0","article-title":"Plasma Interleukin-6 Concentrations, Metabolic Dysfunction, and Asthma Severity: A Cross-Sectional Analysis of Two Cohorts","volume":"4","author":"Peters","year":"2016","journal-title":"Lancet Respir Med"},{"key":"B89","doi-asserted-by":"publisher","first-page":"5105","DOI":"10.1038\/s41598-018-23269-7","article-title":"Dual Role of YM1+ M2 Macrophages in Allergic Lung Inflammation","volume":"8","author":"Draijer","year":"2018","journal-title":"Sci Rep"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02718","article-title":"Non-Redundant Functions of IL-6 Produced by Macrophages and Dendritic Cells in Allergic Airway Inflammation","volume":"9","author":"Gubernatorova","year":"2018","journal-title":"Front Immunol"},{"key":"B91","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/nrd.2018.45","article-title":"Interleukin-6: Designing Specific Therapeutics for a Complex Cytokine","volume":"17","author":"Garbers","year":"2018","journal-title":"Nat Rev Drug Discov"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.026","article-title":"Targeting Interleukin-6 Signaling in Clinic","volume":"50","author":"Kang","year":"2019","journal-title":"Immunity"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.05.026","article-title":"Epithelial IL-6 Trans-Signaling Defines a New Asthma Phenotype With Increased Airway Inflammation","volume":"143","author":"Jevnikar","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/ni.3632","article-title":"Trans-Presentation of IL-6 by Dendritic Cells is Required for the Priming of Pathogenic TH17 Cells","volume":"18","author":"Heink","year":"2017","journal-title":"Nat Immunol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-018-0320-3","article-title":"Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What\u2019s the Difference","volume":"32","author":"Avci","year":"2018","journal-title":"BioDrugs"},{"key":"B96","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1146\/annurev-pharmtox-010611-134715","article-title":"Therapeutic Targeting of the Interleukin-6 Receptor","volume":"52","author":"Tanaka","year":"2012","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxu081","article-title":"Therapeutic Uses of Anti-Interleukin-6 Receptor Antibody","volume":"27","author":"Kang","year":"2015","journal-title":"Int Immunol"},{"key":"B98","doi-asserted-by":"publisher","first-page":"e1044","DOI":"10.1002\/cti2.1044","article-title":"Effects of Interleukin-6 Receptor Blockade on Allergen-Induced Airway Responses in Mild Asthmatics","volume":"8","author":"Revez","year":"2019","journal-title":"Clin Transl Immunol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1804093","article-title":"Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma","volume":"378","author":"Rabe","year":"2018","journal-title":"N Engl J Med"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1080\/14737167.2019.1647104","article-title":"Long-Term Efficacy and Cost-Effectiveness of Infliximab as First-Line Treatment in Rheumatoid Arthritis: Systematic Review and Meta-Analysis","volume":"19","author":"Zrubka","year":"2019","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60250-0","article-title":"Tocilizumab Monotherapy Versus Adalimumab Monotherapy for Treatment of Rheumatoid Arthritis (ADACTA): A Randomised, Double-Blind, Controlled Phase 4 Trial","volume":"381","author":"Gabay","year":"2013","journal-title":"Lancet"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.601842\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T21:00:10Z","timestamp":1699045210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.601842\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,18]]},"references-count":101,"alternative-id":["10.3389\/fimmu.2021.601842"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.601842","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,18]]},"article-number":"601842"}}