Impact Of IL-4 Research Articles

The Impact of IL-4 on Abortion Rates in Iraqi Women's Last Trimester Pregnancies

The term "abortion" is used to describe the termination of a pregnancy through the surgical expulsion of a developing embryo or fetus. Whole samples were collected from Al-Zahraa Teaching Hospital in Wasit city From mid-October 2022 until mid-October 2023. The total number of samples was 100 divided into two groups: the first group is women who suffer from a miscarriage in the third trimester and the control group .Result: This table shows the interpretation of the results between patients and healthy people, where the homozygous CC genotype significantly decreased comparing with control (64 versus 86%, OR=0.18; p-value =0.03 ), while the CT heterozygous genotype was significantly high with risk in comparison with control (32 versus 8%; OR= 7.3; p-value 0.005). The study of polymorphism of the IL-4 gene and its association with abortion had limited available data. This study is the second to report on the association between polymorphism of IL-4 and abortion. showed a clear difference of the parameter’s levels in abortion study group. Based on the mutant homozygous CC genotype. In the present study, the significant change in IL-4 concentration was observed due to the effect of the polymorphism in cases of abortion. These findings were consistent with a previous study that reported higher concentrations of IL-4 in women with abortion compared to normal women (P-value of 0.001). (Association between maternal circulating IL-4 levels and preeclampsia).

Abstract 634: The impact of IL-4 on migration in triple negative breast cancer cell lines

Abstract In the United States, triple-negative breast cancer (TNBC), an aggressive form of breast cancer (BCa), disproportionately affects women of African descent and contributes to racial disparities in BCa mortality. Various risk factors are thought to drive this disparity, including socioeconomic status, tumor characteristics, comorbidities, and quality of treatment. Complex diseases and environmental insults all invoke and/or disrupt host inflammation, with individual immune and variable responses to therapeutic agents being dictated in part by genetic variants. This latter has seldom been studied with regards to precision diagnosis and prognosis of individual patient responses, in the frame of geographical ancestry and TNBC. Interleukin-4 receptors (IL4R) have been shown to be upregulated in many epithelial cancers and could be a promising target for metastatic tumor therapy. Yet, IL4R overexpression and/or IL4R variants have not been evaluated in TNBC cell lines of varying genetic ancestry. In view of this, we investigated the effects of IL-4 treatment in four TNBC cell lines varying in proportions of West African Ancestry (WAA) in each cell line: MDA-MB-231 (0.019), HCC-1143 (0.012), HCC-1806 (0.807), MDA-MB-468 (0.803). The frequency of IL4R variants also differed in each cell line. We used high content live cell imaging to evaluate the effect of IL-4 treatment on cellular migration by measuring wound healing. We show that IL-4 treatment on TNBC cells enhances migration as indicated by increased wound healing when compared to non-treated cells. High glucose, at a concentration of 10 g/L, delays cell migration in IL4-treated TNBC cells. This data suggests that comorbidities, such as high glucose levels (i.e., uncontrolled diabetes) could impact tumor behavior and mortality disparities between populations. Citation Format: Portia Andrews, Kevin S. Kimbro. The impact of IL-4 on migration in triple negative breast cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 634.

IL-4 enhances interferon production by virus-infected human mast cells

IL-4 enhances interferon production by virus-infected human mast cells

The impact of IL-4 on the CD8 T cell response to infection (P4483)

Abstract IL-4 influences the development of memory-phenotype, IFNγ-producing, CD8 T cells and plays a critical role in the generation of antigen-specific memory cells during liver-stage malaria infection. Elevated IL-4 levels, which can be efficiently created by treatment with IL-4 cytokine-antibody complexes (IL-4C), enhances the number of CD8 memory T cells displaying high expression of CXCR3 and Eomes, but low levels of T-bet. This is in contrast to treatment with IL-2 cytokine-antibody complexes (IL-2C) that generate T-bet high, Eomes and CXCR3 low, and granzyme B expressing cells. IL-2C and IL-4C also caused differential responses to an acute pathogen. Whereas IL-2C treatment of naïve C57BL/6 mice produced a significant improvement in clearance of Listeria monocytogenes(LM) infection, IL-4C failed to have an effect, despite a large expansion of the CD8 memory pool. Interestingly, BALB/c mice, which are known as a “Type-2” or naturally IL-4 high mouse strain, demonstrated better clearance of LM after IL-4C treatment. This suggests that depending on the mouse strain, there may be intrinsically different CD8 T cell signals generated in response to γc cytokines, with global functional consequences for the host. Future studies will explore both the functional significance of IL-4 at different stages of the CD8 T cell response to LM and malaria and ask whether IL-4C treatment is able to augment immunity.

Negative Regulation of NKG2D Expression by IL-4 in Memory CD8 T Cells

IL-4 is one of the main cytokines produced during Th2-inducing pathologies. This cytokine has been shown to affect a number of immune processes such as Th differentiation and innate immune responses. However, the impact of IL-4 on CD8 T cell responses remains unclear. In this study, we analyzed the effects of IL-4 on global gene expression profiles of Ag-induced memory CD8 T cells in the mouse. Gene ontology analysis of this signature revealed that IL-4 regulated most importantly genes associated with immune responses. Moreover, this IL-4 signature overlapped with the set of genes preferentially expressed by memory CD8 T cells over naive CD8 T cells. In particular, IL-4 downregulated in vitro and in vivo in a STAT6-dependent manner the memory-specific expression of NKG2D, thereby increasing the activation threshold of memory CD8 T cells. Furthermore, IL-4 impaired activation of memory cells as well as their differentiation into effector cells. This phenomenon could have an important clinical relevance as patients affected by Th2 pathologies such as parasitic infections or atopic dermatitis often suffer from viral-induced complications possibly linked to inefficient CD8 T cell responses.

Alternatively activated dendritic cells regulate CD4+ T-cell polarization in vitro and in vivo.

Interleukin-4 is a cytokine widely known for its role in CD4(+) T cell polarization and its ability to alternatively activate macrophage populations. In contrast, the impact of IL-4 on the activation and function of dendritic cells (DCs) is poorly understood. We report here that DCs respond to IL-4 both in vitro and in vivo by expression of multiple alternative activation markers with a different expression pattern to that of macrophages. We further demonstrate a central role for DC IL-4Rα expression in the optimal induction of IFNγ responses in vivo in both Th1 and Th2 settings, through a feedback loop in which IL-4 promotes DC secretion of IL-12. Finally, we reveal a central role for RELMα during T-cell priming, establishing that its expression by DCs is critical for optimal IL-10 and IL-13 promotion in vitro and in vivo. Together, these data highlight the significant impact that IL-4 and RELMα can have on DC activation and function in the context of either bacterial or helminth pathogens.

Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups living in Mali

This study aimed to examine the effect of IL-4 -590 T/C polymorphism on the levels of malaria-specific IgE, IgG, IgG (1–4) subclasses as well as total IgE in the Fulani and their sympatric ethnic group, the Dogon, in Mali. Asymptomatic individuals, of the Fulani and the Dogon ethnic groups, were included in the study. IL-4 is involved in the regulation of IgE and IgG4 subclass. In line with this we found that within the Fulani, the T allele was associated with increased levels of total and anti-malarial IgE ( P = 0.02 and P = 0.04, respectively). The Fulani T allele carriers had slightly higher levels of malarial specific IgG4 as compared to those with the CC genotype ( P = 0.08). No such differences were observed amongst the Dogon individuals. Taken together, these data indicate that the impact of IL-4 -590 variants on antibody levels may vary in different ethnic populations, and that this might affect the Ig-class and subclass distributions.

IL-4 down-regulates the responsiveness of human intraepithelial lymphocytes.

IL-4 is an important regulator of intestinal inflammation, yet little is known regarding its action on intestinal lymphocytes. Intestinal lymphocytes were isolated from jejunal mucosa of patients undergoing gastric bypass operations for morbid obesity. The impact of IL-4 was measured by its effects on proliferation using 3H-thymidine incorporation, IL-2 production using the CTLL assay, and IL-2 receptor generation using immunofluorescence. The production of IL-4 was measured by ELISA. IL-4 significantly inhibited the proliferation of intraepithelial lymphocytes (IEL) to a variety of stimuli as well as the development of lymphokine-activated killer (LAK) cells. In contrast, it had no effect on the proliferation of CD8+ T cells from peripheral blood. The inhibitory effect of IL-4 on IEL did not occur during activation, since IL-2 production and receptor expression were not altered. Rather, it occurred during cell cycling, since over 50% inhibition resulted whether IL-4 was added at the initiation of an IL-2-stimulated culture or after 24 or 48 h incubation. IL-4 was secreted by activated lamina propria lymphocytes (LPL) but not by IEL. IL-4, produced by activated LPL, may enter the epithelial compartment and down-regulate responsiveness of IEL.