Isosorbide fatty acid diesters have synergistic anti-inflammatory effects in cytokine-induced tissue culture models of atopic dermatitis. Isosorbide fatty acid diesters have synergistic anti-inflammatory effects in cytokine-induced tissue culture models of atopic dermatitis

Atopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (IDL) and isosorbide dicaprylate (IDC), using AD-like tissue culture models. Treatment of reconstituted human epidermis with cytokine cocktail (IL-4 + IL-13 + TNF-α + IL-31) compromised the epidermal barrier, but this was prevented by co-treatment with IDL and IDC. Cytokine stimulation also dysregulated expression of keratinocyte (KC) differentiation genes whereas treatment with IDC or IDL+IDC up-regulated genes associated with early (but not late) KC differentiation. Although neither IDL nor IDC inhibited Th2 cytokine responses, both compounds repressed TNF-α-induced genes and IDL+IDC led to synergistic down-regulation of inflammatory (IL1B, ITGA5) and neurogenic pruritus (TRPA1) mediators. Treatment of cytokine-stimulated skin explants with IDC decreased lactate dehydrogenase (LDH) secretion by more than 50% (more than observed with cyclosporine) and in vitro LDH activity was inhibited by IDL and IDC. These results demonstrate anti-inflammatory mechanisms of isosorbide fatty acid diesters in AD-like skin models. Our findings highlight the multifunctional potential of plant oil derivatives as topical ingredients and support studies of IDL and IDC as therapeutic candidates. Overall design: Microarray analyses were performed on reconstituted human epidermis (RHE) samples treated with caprylic/capric triglyceride vehicle only (CTL), cytokine cocktail (CYT), cytokines with 4% IDL (CYT+IDL), cytokines with 4% IDC (CYT+IDC) or cytokines with 2% IDL and 2% IDC (CYT+IDL+IDC) (n = 3 replicates per group).