The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention

Jayalatha, Akshaya Keerthi Saikumar; Hesse, Laura; Ketelaar, Marjolijn; Koppelman, Gerard H.; Nawijn, Martijn C.

doi:10.1016/j.pharmthera.2021.107847

Cited by 82 publications

(81 citation statements)

References 230 publications

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“…Interleukin-33 (IL-33) is a ligand for ST2, a member of the Toll-like / interleukin-1 receptor superfamily, which is associated with the accessory protein IL-1RAcP [8]. After activation of ST2 / IL-1RAcP by interleukin-33, the signaling cascade is stimulated by lowerlevel molecules such as MyD88 (myeloid differentiation factor 88) and TRAF6 (tumor necrosis factor receptor binding factor 6), which leads to among other things, to the activation of NFKB (nuclear factor-kB).…”

Section: Research Resultsmentioning

confidence: 99%

Prognostic value of ST2 biomarkers in hypertonic disease patients on the background of the chronic obstructive pulmonary disease

Kraydashenko

Tyaglaya

2021

J Educ Health Sport

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Introduction. Scientific research by domestic and foreign scientists and many years of clinical experience suggests that in patients with chronic obstructive pulmonary disease (COPD) a combination with arterial hypertension (AH) were often observed. Soluble form of ST2 protein of the patients is involved in certain inflammatory diseases and in the paracrine system of protection of the heart and lungs as marker, that determines the prognosis in patients with heart and lung deficiency and predicts the death of the patient during the year. The purpose of this study was to evaluate the expression of ST2 protein in patients with arterial hypertension on the background of chronic obstructive pulmonary disease. Materials and methods. In 23 patients were diagnosed arterial hypertension stage II and COPD stage II without clinically significant concomitant disease, with an average age 51.72 ± 1.22 years (49.33-54.09) (gender composition: 22 males and 1 female), the smoking status is comparable to COPD patients, 18 patients with AH of both sexes aged from 33 to 67 years (mean age 50.74 ± 1.49 years (47.81-53.76), male / female ratio 17 / 83%), stage II of the arterial hypertension with the level of I-III degree of hypertension, different cardiovascular risk, without adequate systematic antihypertensive therapy and 18 patients with COPD stage II, mean age 50.32 ± 0.99 years (48.22-52.16) (gender composition: 14 males and 4 females), duration of the disease 7.52 ± 1.14 years. 80% of active smokers, the index of bacon-years 17.23 ± 2.69 years, the harmful professional factors (industrial) indicated 23.53%. Participants expressed their willingness to be included in medical research. Research results. The obtained data indicate that the lowest level of expression of ST2 protein was detected in patients with hypertension without concomitant pathology – 21.05 ± 2.12 ng/mL, which is in 11.78% lower than in patients with COPD without concomitant pathology (23,53 ± 1.8 ng/mL). The highest expression of ST2 protein were demonstrated in patients with comorbid pathology group with COPD on the background of AH – 33.01 ± 6.25 ng/mL, which is in 56.82% higher compared with patients with AH, and in 40.29% higher than analogous marker in patients with monopathology in the form of COPD. In the group of COPD patients with a high level of ST2 (more than 30 ng / ml), significantly more negatively controlled negative cardiovascular predictors, such as the presence of left ventricular hypertrophy (χ2 = 7.61 at p = 0.006) and sympathetic balance disturbances according to the LF / HF index (χ2 = 4.72 at p = 0.03) and ST2 elevation was reliably associated not only with extrapulmonary prognostic factors, but also with a decrease in FEV1 of less than 50% (χ2 = 5.45 at p = 0.02). Conclusions. Patients of the experimental group with comorbid pathology AH and COPD had the most significant increasing level of ST2 protein as unfavorable prognosis marker compared to the groups of patients without combination of this pathology.

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Section: Research Resultsmentioning

confidence: 99%

Prognostic value of ST2 biomarkers in hypertonic disease patients on the background of the chronic obstructive pulmonary disease

Kraydashenko

Tyaglaya

2021

J Educ Health Sport

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“…Anti-IL-33 mabs in clinical trials for AD and/or asthma are etokimab (ANB020), itepekimab (REGN 3500), astegolimab (MSTT1041A/ AMG282), and tozorakimab [ 3 ]. In asthma, itepekimab improved lung function, asthma control and quality of life, and led to a greater reduction of eosinophils compared to placebo [ 133 , 141 ]. Results of RCTs with itepekimab and astegolimab for AD have not been published yet.…”

Section: Implications For Preventive and Therapeutic Interventionsmentioning

confidence: 99%

From Skin Barrier Dysfunction to Systemic Impact of Atopic Dermatitis: Implications for a Precision Approach in Dermocosmetics and Medicine

Maintz

Bieber

Simpson³

et al. 2022

JPM

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: Atopic dermatitis (AD) affects up to 20% of children and is considered the starting point of the atopic march with the development of food allergy, asthma, and allergic rhinitis. The heterogeneous phenotype reflects distinct and/or overlapping pathogenetic mechanisms with varying degrees of epidermal barrier disruption, activation of different T cell subsets and dysbiosis of the skin microbiome. Here, we review current evidence suggesting a systemic impact of the cutaneous inflammation in AD together with a higher risk of asthma and other comorbidities, especially in severe and persistent AD. Thus, early therapy of AD to restore the impaired skin barrier, modified microbiome, and target type 2 inflammation, depending on the (endo)phenotype, in a tailored approach is crucial. We discuss what we can learn from the comorbidities and the implications for preventive and therapeutic interventions from precision dermocosmetics to precision medicine. The stratification of AD patients into biomarker-based endotypes for a precision medicine approach offers opportunities for better long-term control of AD with the potential to reduce the systemic impact of a chronic skin inflammation and even prevent or modify the course, not only of AD, but possibly also the comorbidities, depending on the patient’s age and disease stage.

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“…Thus, IL-33 plays a major role in the initiation and development of type 2 immune responses, which are essential during host infection by helminths for example [ 27 , 111 , 112 ], but which, on the other hand, contribute to the development of various allergic diseases, such as asthma or atopic dermatitis. The precise role of IL-33 in these pathologies and its mechanism of action have been widely described in various reviews [ 90 , 91 , 96 , 113 , 114 , 115 , 116 , 117 ]. Importantly, IL-33 plays a major role in human asthma, since the IL33 and IL1RL1 genes have been identified, on a recurrent basis, as susceptibility genes for asthma in very large genetic studies [ 118 , 119 ] (for reviews, see [ 17 , 120 , 121 ]).…”

Section: The Il-33/st2l Axis: From Discovery To Functionmentioning

confidence: 99%

IL-33, an Alarmin of the IL-1 Family Involved in Allergic and Non Allergic Inflammation: Focus on the Mechanisms of Regulation of Its Activity

Cayrol

2021

Cells

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Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) family that is expressed in the nuclei of endothelial and epithelial cells of barrier tissues, among others. It functions as an alarm signal that is released upon tissue or cellular injury. IL-33 plays a central role in the initiation and amplification of type 2 innate immune responses and allergic inflammation by activating various target cells expressing its ST2 receptor, including mast cells and type 2 innate lymphoid cells. Depending on the tissue environment, IL-33 plays a wide variety of roles in parasitic and viral host defense, tissue repair and homeostasis. IL-33 has evolved a variety of sophisticated regulatory mechanisms to control its activity, including nuclear sequestration and proteolytic processing. It is involved in many diseases, including allergic, inflammatory and infectious diseases, and is a promising therapeutic target for the treatment of severe asthma. In this review, I will summarize the literature around this fascinating pleiotropic cytokine. In the first part, I will describe the basics of IL-33, from the discovery of interleukin-33 to its function, including its expression, release and signaling pathway. The second part will be devoted to the regulation of IL-33 protein leading to its activation or inactivation.

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The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention

Cited by 82 publications

References 230 publications

Prognostic value of ST2 biomarkers in hypertonic disease patients on the background of the chronic obstructive pulmonary disease

Prognostic value of ST2 biomarkers in hypertonic disease patients on the background of the chronic obstructive pulmonary disease

From Skin Barrier Dysfunction to Systemic Impact of Atopic Dermatitis: Implications for a Precision Approach in Dermocosmetics and Medicine

IL-33, an Alarmin of the IL-1 Family Involved in Allergic and Non Allergic Inflammation: Focus on the Mechanisms of Regulation of Its Activity

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