Novel Anti-Cytokine Strategies for Prevention and Treatment of Respiratory Allergic Diseases

被引:26
作者
Gubernatorova, Ekaterina O. [1 ,2 ]
Namakanova, Olga A. [1 ,2 ]
Gorshkova, Ekaterina A. [2 ,3 ]
Medvedovskaya, Alexandra D. [1 ,2 ]
Nedospasov, Sergei A. [1 ,2 ,3 ,4 ]
Drutskaya, Marina S. [1 ,3 ]
机构
[1] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia
[2] Lomonosov Moscow State Univ, Moscow, Russia
[3] Russian Acad Sci, Ctr Precis Genome Editing & Genet Technol Biomed, Engelhardt Inst Mol Biol, Moscow, Russia
[4] Sirius Univ Sci & Technol, Dept Immunobiol & Biomed, Soci, Russia
基金
俄罗斯科学基金会;
关键词
anti-IL-6; anti-TNF; anticytokine therapy; severe asthma; combined cytokine targeting; alarmins in asthma; NECROSIS-FACTOR-ALPHA; MURINE MODEL; IL-6; MACROPHAGES; NEUTROPHIL; ASTHMA; CELLS;
D O I
10.3389/fimmu.2021.601842
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Asthma is a heterogeneous 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.
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页数:9
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