Interleukin-4 as a therapeutic target

Gärtner, Yvonne; Bitar, Lynn; Zipp, Frauke; Vogelaar, Christina Francisca

doi:10.1016/j.pharmthera.2023.108348

Cited by 25 publications

(12 citation statements)

References 137 publications

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“…IL-4 is a cytokine that plays a key role in type 2 immune response, especially in the context of allergic inflammation or parasitic invasion [ 49 , 50 ]. It serves as an immunoregulatory agent, associated with mediating allergy reactions through encouraging B cell production of Immunoglobulin E (IgE) and Th2 lymphocyte development [ 51 , 52 ].…”

Section: Resultsmentioning

confidence: 99%

The Role of Selected Interleukins in the Development and Progression of Multiple Sclerosis—A Systematic Review

Grunwald,

Krętowska-Grunwald,

Adamska-Patruno

et al. 2024

IJMS

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Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple sclerosis remains an incurable disease, the management of MS predominantly focuses on reducing relapses and decelerating the progression of both physical and cognitive decline. The continuous autoimmune process modulated by cytokines seems to be a vital contributing factor to the development and relapse of multiple sclerosis. This review sought to summarize the role of selected interleukins in the pathogenesis and advancement of MS. Patients with MS in the active disease phase seem to exhibit an increased serum level of IL-2, IL-4, IL-6, IL-13, IL-17, IL-21, IL-22 and IL-33 compared to healthy controls and patients in remission, while IL-10 appears to have a beneficial impact in preventing the progression of the disease. Despite being usually associated with proinflammatory activity, several studies have additionally recognized a neuroprotective role of IL-13, IL-22 and IL-33. Moreover, selected gene polymorphisms of IL-2R, IL-4, IL-6, IL-13 and IL-22 were identified as a possible risk factor related to MS development. Treatment strategies of multiple sclerosis that either target or utilize these cytokines seem rather promising, but more comprehensive research is necessary to gain a clearer understanding of how these cytokines precisely affect MS development and progression.

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Section: Resultsmentioning

confidence: 99%

The Role of Selected Interleukins in the Development and Progression of Multiple Sclerosis—A Systematic Review

Grunwald,

Krętowska-Grunwald,

Adamska-Patruno

et al. 2024

IJMS

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“…IL-2 enhances T-lymphocyte activity, improving body immunity ( Shapiro MR et al, 2023 ). IL-4 activate the humoral immune response, induce the expression of immunoglobulin IgG and reduces inflammation ( Gärtner et al, 2023 ). TNF-α promotes the body’s ability to resist infection by pathogenic microorganisms and promoting mucosal immune protection ( El-Gindy YM et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Preparation and activity study of Ruoqiang jujube polysaccharide copper chelate

Moheteer,

Li,

Abulikemu

et al. 2024

Front. Pharmacol.

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Background: Polysaccharide metal chelate exhibit both immunoregulatory activity and metal element supplementation effects.Methods: In this study, Ruoqiang jujube polysaccharide copper chelate (RJP-Cu) was prepared and the preparation conditions were optimized using the response surface method. Subsequently, RJP-Cu was administered to lambs to evaluate its impact on growth performance, copper ion (Cu2+) supplementation, immune enhancement, and intestinal flora was evaluated.Results: The results indicated that optimal RJP-Cu chelation conditions included a sodium citrate content of 0.5 g, a reaction temperature of 50°C, and a solution pH of 8.0, resulting in a Cu2+ concentration of 583°mg/kg in RJP-Cu. Scanning electron microscopy (SEM) revealed significant structural changes in RJP before and after chelation. RJP-Cu displaying characteristic peaks of both polysaccharides and Cu2+ chelates. Blood routine indexes showed no significant differences among the RJP-Cu-High dose group (RJP-Cu-H), RJP-Cu-Medium dose group (RJP-Cu-M), RJP-Cu-low dose group (RJP-Cu-L) and the control group (p > 0.05). However, compared with the control group, the RJP-Cu-H, M, and L dose groups significantly enhanced lamb production performance (p < 0.05). Furthermore, RJP-Cu-H, M, and L dose groups significantly increased serum Cu2+ concentration, total antioxidant capacity (T-AOC), catalase (CAT), and total superoxide dismutase (T-SOD) contents compared with control group (p < 0.05). The RJP-Cu-H group exhibited significant increases in serum IgA and IgG antibodies, as well as the secretion of cytokines IL-2, IL-4, and TNF-α compared to the control group (p < 0.05). Furthermore, RJP-Cu-H group increased the species abundance of lamb intestinal microbiota, abundance and quantity of beneficial bacteria, and decrease the abundance and quantity of harmful bacteria. The RJP-Cu-H led to the promotion of the synthesis of various Short Chain Fatty Acids (SCFAs), improvements in atrazine degradation and clavulanic acid biosynthesis in lambs, while reducing cell apoptosis and lipopolysaccharide biosynthesis.Conclusion: Thus, these findings demonstrate that RJP-Cu, as a metal chelate, could effectively promote lamb growth performance, increase Cu2+ content, and potentially induce positive immunomodulatory effects by regulating antioxidant enzymes, antibodies, cytokines, intestinal flora, and related metabolic pathways.

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“…Traditionally, IL-4 was reported as an anti-in ammatory interleukin recognized to polarize T cells to their Th2 phenotype [33][34][35]. Considering the potential positive causal effect on bronchodilation, it should be mentioned that IL-4 plays a positive role in airway in ammation and acts on lung function decline, while IL-4 shows its effects as an anti-in ammatory target [36,37]. Ying Liu et al also found that NLRP3 promotes asthma and in ammation by upregulating the expression of IL-4, and Martijn L Manson et al reported that IL-4 induces hyperresponsiveness in isolated human small airways [38,39].…”

Section: Discussionmentioning

confidence: 99%

Exploring Causal Cytokines and Potential Regulatory Genes in Bronchiectasis: Findings from Mendelian randomization

Liao,

Zhou,

Lin

et al. 2023

Preprint

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Background Bronchiectasis is a chronic respiratory disease characterized by irreversible dilation of the bronchi, which leads to impaired mucociliary clearance, recurrent infections, and inflammatory responses. Despite advancements in diagnostic techniques and therapeutic strategies, the underlying etiological factors driving bronchiectasis pathogenesis remain incompletely elucidated. Methods Genome-wide data were utilized to conduct two-sample Mendelian randomization focusing on the causality from 41 inflammatory factors on bronchiectasis. Sensitivity tests were carried out to validate the reliability. SMR, coloc, and intermediary Mendelian randomization were utilized to determine latent upstream genes and estimate indirect effects. Results Four inflammatory factors’ potential causal effects on bronchiectasis were identified: MMIF (0.85 (0.74, 0.98) 0.029), IL-4 (1.32 (1.09, 1.55) 0.019), IFN-γ (1.28 (1.02, 1.60) 0.032), and FGF-Basic (1.28 (1.03, 1.59) 0.025) (FinnGen R9, IVW, reported as OR (95% CI) P). Sensitivity tests supported the direction consistency of IFN-γ and FGF-Basic’s estimates instead of MMIF and IL-4. RP11-589P10.5 was found to reduce the risk of bronchiectasis, mediated by the IFN-γ concentration (OR = 0.96, proportion = 36.52%). Conclusions Our study has identified strong evidence for potential positive causalities from IFN-γ and FGF-Basic. RP11-589P10.5 was found to latently decrease the risk of bronchiectasis, which is mediated by IFN-γ. At the genetic level, we anticipate that the cytokines and the gene can be taken into account in predictive models for bronchiectasis and even as indicators of the severity of the disease, providing new directions for future population research and basic experiments related to bronchiectasis.

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Interleukin-4 as a therapeutic target

Cited by 25 publications

References 137 publications

The Role of Selected Interleukins in the Development and Progression of Multiple Sclerosis—A Systematic Review

The Role of Selected Interleukins in the Development and Progression of Multiple Sclerosis—A Systematic Review

Preparation and activity study of Ruoqiang jujube polysaccharide copper chelate

Exploring Causal Cytokines and Potential Regulatory Genes in Bronchiectasis: Findings from Mendelian randomization

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