Atopic Patients Show Increased Interleukin 4 Plasma Levels but the Degree of Elevation Is Not Sufficient to Upregulate Interleukin-4-Sensitive Genes

Abstract

<b><i>Background:</i></b> Atopic diseases constitute a major health challenge for industrialized countries, and elevated levels of interleukin 4 (IL-4) frequently characterize these disorders. Previous in vitro<i></i>analyses have indicated that IL-4 strongly upregulates the expression of IL-4-sensitive genes in human monocytes. <b><i>Objective:</i></b> To explore whether similar expression alterations may contribute to the pathomechanisms of atopic diseases in vivo we carried out a small-scale case-control clinical study (<i>n</i> = 43), in which we quantified the plasma levels of IgE and IL-4 as well as the expression of selected IL-4-sensitive genes in blood leukocytes. <b><i>Methods:</i></b> 34 allergic patients suffering from allergic rhinitis (<i>n</i> = 11), atopic eczema (<i>n</i> = 11) and allergic asthma (<i>n</i> = 12) as well as 9 healthy control individuals were recruited. IgE and IL-4 plasma levels were determined by ELISA, and the expression of selected IL-4-sensitive gene products in blood leukocytes was quantified by qRT-PCR. In addition, the fatty acid oxygenase activity of isolated monocytes was measured by RP-HPLC analysis of the arachidonic acid oxygenation products (ex vivo activity assays). <b><i>Results:</i></b> We found that plasma levels of IgE and IL-4 were significantly elevated in atopic patients but the degree of elevation was not sufficient to upregulate the expression of the selected IL-4-sensitive genes in circulating leukocytes. Moreover, the arachidonic acid oxygenase activity of blood monocytes was not significantly altered in atopic patients. <b><i>Conclusion:</i></b> Our data suggest that the IL-4 plasma levels of atopic patients are not high enough to impact the expression of IL-4-sensitive genes.

Tralokinumab in atopic dermatitis

“…genes demonstrated in vitro [9]. As a consequence, biologics that target IL-13 alone may be efficacious for controlling AD.…”

“…The overexpression of IL‐13 in AD skin contributes to the vicious cycle of inflammation, skin‐barrier dysfunction, and microbiome dysbiosis [5, 6]. In addition, it has been suggested that in vivo IL‐4 levels are not high enough to impact the expression of IL‐4‐sensitive genes demonstrated in vitro [9]. As a consequence, biologics that target IL‐13 alone may be efficacious for controlling AD.…”

“…Dupilumab, an antibody that binds to IL-4 receptor (IL-4Rα) and prevents both IL-4 and IL-13 signaling, is currently approved for the treatment of AD, asthma and chronic rhinosinusitis with polyposis. Recent studies have identified IL-13 to be the most abundant type 2 cytokine in AD lesional skin and the expression levels of IL-13 in lesional skin correlate with disease severity [5][6][7][8][9]. The overexpression of IL-13 in AD skin contributes to the vicious cycle of inflammation, skin-barrier dysfunction, and microbiome dysbiosis [5,6].…”

Tralokinumab bei atopischer Dermatitis

“…Dupilumab, ein Antikörper der an den IL-4-Rezeptor (IL-4Rα) bindet und sowohl IL-4-als auch IL-13-Signale verhindert, ist gegenwärtig für die Behandlung von AD, Asthma und chronischer Rhinosinusitis mit Polyposis zugelassen. In neueren Studien wurde IL-13 als häufigstes Typ-2-Zytokin in läsionaler Haut bei AD identifiziert, wobei das Expressionsniveau von IL-13 in den Hautläsionen mit der Schwere der Erkrankung korreliert [5][6][7][8][9]. Die Überexpression von IL-13 in der AD-Haut trägt zum Teufelskreis von Entzündung, Störung der Hautbarriere und Dysbiose des Mikrobioms bei [5,6].…”

“…Die Überexpression von IL-13 in der AD-Haut trägt zum Teufelskreis von Entzündung, Störung der Hautbarriere und Dysbiose des Mikrobioms bei [5,6]. Außerdem wird vermutet, dass die Konzentration von IL-4 in vivo nicht hoch genug ist, um die, in vitro nachgewiesene, Expression IL-4-sensitiver Gene zu beeinflussen [9]. Folglich können Biologika, die gezielt nur gegen IL-13 gerichtet sind, AD möglicherweise wirksam kon-trollieren.…”