Single and Synergistic Effects of Type 2 Cytokines on Eosinophils and Asthma Hallmarks

Abstract

The type 2 cytokines IL-5, IL-13, and IL-4 play an important role in the induction and progression of asthma. According to the Global Initiative for Asthma guidelines, blood eosinophil numbers are one marker that helps to guide treatment decisions in patients suffering from severe forms of asthma. Effects of type 2 cytokines were analyzed, alone or in combination, on eosinophils in blood and other compartments and on the development of asthma symptoms. C57BL/6 mice received a single intranasal application of equimolar amounts of IL-5, IL-13, and IL-4, alone or in combination. Numbers, activation state, and migratory behavior of eosinophils in bone marrow (BM), blood, lung, and bronchoalveolar lavage as well as airway hyperresponsiveness and goblet cell metaplasia were evaluated. Only IL-13 was associated with airway eosinophilia, development of airway hyperresponsiveness, and goblet cell metaplasia, without any synergistic effects. IL-5 increased the number of eosinophils in BM and lung tissue but failed to affect structural changes. IL-4 had similar, but weaker, effects to IL-13. Cytokine combinations synergistically affected eosinophils but failed to enhance IL-13–driven effects on lung function or goblet cell metaplasia. IL-5 and IL-13 markedly increased eosinophil numbers locally in lung and airways and distally in blood and BM, whereas IL-5 and IL-4 only increased eosinophils in lung and BM. IL-13 together with IL-4 failed to demonstrate any synergistic effect. These insights into single and combined effects of type 2 cytokines on disease-driving mechanisms could improve understanding of the impact and effectiveness of new therapies in asthma.

Precision medicine reaching out to the patients in allergology – a German-Japanese workshop report

“…Experimental data suggests that IL-5 is important for the increase in all compartments of the body. In contrast, IL-4 and IL-13 in the lung lead to an increased recruitment of eosinophils into the lung [ 25 ]. So far it is unclear which of these patients will respond best to either IL-5R blockade or IL-4Rα blockade, and further studies are needed to identify parameters which will help to choose the right antibody for the right patients.…”

Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities

“…IL-4 also induces the expression of VCAM-1 and eotaxin by epithelial cells which enhances eosinophil migration to the site of allergic inflammation (16). study by Beckert et al, provides evidence on the effects of the Th2 cytokines, either alone or in combination, on eosinophils in a mouse model (56). C57BL/6 mice were intranasally administered equimolar amounts of single agent or combination IL-4, IL-5 and IL-13.…”

Pulmonary Eosinophils at the Center of the Allergic Space-Time Continuum

“…Following the initial release of type 2 cytokines in the lung (by ILC2 and NKT cells), activated eosinophils upregulate multiple cell surface receptors, allowing them to become dynamically regulated and in turn drive the production of canonical Th2 cytokines IL-4, IL-5, and IL-13 by T cells ( 146 ). A systematic investigation of these cytokines revealed single and synergistic effects on eosinophils and lung inflammatory hallmarks, such as goblet cell metaplasia ( 147 ). Over time, plasma cells arise.…”