Therapeutic Potential of Combining IL-6 and TNF Blockade in a Mouse Model of Allergic Asthma
Combined anti-cytokine therapy is a promising therapeutic approach for uncontrolled steroid-resistant asthma. In this regard, simultaneous blockade of IL-4 and IL-13 signaling by Dupilumab (anti-IL-4Ra monoclonal antibody) was recently approved for severe eosinophilic asthma. However, no therapeutic options for neutrophilic asthma are currently available. Recent advances in our understanding of asthma pathogenesis suggest that both IL-6 and TNF may represent potential targets for treatment of severe neutrophilic asthma. Nevertheless, the efficacy of simultaneous pharmacological inhibition of TNF and IL-6 in asthma was not yet studied. To evaluate the potency of combined cytokine inhibition, we simultaneously administrated IL-6 and TNF inhibitors to BALB/c mice with HDM-induced asthma. Combined IL-6/TNF inhibition, but not individual blockade of these two cytokines, led to complex anti-inflammatory effects including reduced Th2-induced eosinophilia and less prominent Th17/Th1-mediated neutrophilic infiltrate in the airways. Taken together, our results provide evidence for therapeutic potential of combined IL-6/TNF inhibition in severe steroid-resistant asthma.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 23(2022), 7 vom: 24. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Namakanova, Olga A [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Anti-cytokine therapy |
|---|
| Anmerkungen: |
Date Completed 13.04.2022 Date Revised 31.05.2022 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms23073521 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM339384883 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM339384883 | ||
| 003 | DE-627 | ||
| 005 | 20231226002758.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms23073521 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1131.xml |
| 035 | |a (DE-627)NLM339384883 | ||
| 035 | |a (NLM)35408882 | ||
| 035 | |a (PII)3521 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Namakanova, Olga A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Therapeutic Potential of Combining IL-6 and TNF Blockade in a Mouse Model of Allergic Asthma |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.04.2022 | ||
| 500 | |a Date Revised 31.05.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Combined anti-cytokine therapy is a promising therapeutic approach for uncontrolled steroid-resistant asthma. In this regard, simultaneous blockade of IL-4 and IL-13 signaling by Dupilumab (anti-IL-4Ra monoclonal antibody) was recently approved for severe eosinophilic asthma. However, no therapeutic options for neutrophilic asthma are currently available. Recent advances in our understanding of asthma pathogenesis suggest that both IL-6 and TNF may represent potential targets for treatment of severe neutrophilic asthma. Nevertheless, the efficacy of simultaneous pharmacological inhibition of TNF and IL-6 in asthma was not yet studied. To evaluate the potency of combined cytokine inhibition, we simultaneously administrated IL-6 and TNF inhibitors to BALB/c mice with HDM-induced asthma. Combined IL-6/TNF inhibition, but not individual blockade of these two cytokines, led to complex anti-inflammatory effects including reduced Th2-induced eosinophilia and less prominent Th17/Th1-mediated neutrophilic infiltrate in the airways. Taken together, our results provide evidence for therapeutic potential of combined IL-6/TNF inhibition in severe steroid-resistant asthma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HDM-induced asthma | |
| 650 | 4 | |a Th17/Th1-induced neutrophilia | |
| 650 | 4 | |a Th2-induced eosinophilia | |
| 650 | 4 | |a anti-cytokine therapy | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 700 | 1 | |a Gorshkova, Ekaterina A |e verfasserin |4 aut | |
| 700 | 1 | |a Zvartsev, Ruslan V |e verfasserin |4 aut | |
| 700 | 1 | |a Nedospasov, Sergei A |e verfasserin |4 aut | |
| 700 | 1 | |a Drutskaya, Marina S |e verfasserin |4 aut | |
| 700 | 1 | |a Gubernatorova, Ekaterina O |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 23(2022), 7 vom: 24. März |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:23 |g year:2022 |g number:7 |g day:24 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms23073521 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 23 |j 2022 |e 7 |b 24 |c 03 | ||