Anti-inflammatory and moisturizing properties of an active complex in the modulation of markers associated to Atopic Dermatitis

Author: Samara Eberlin

Published at: September 12, 2018

27th EADV (European Academy of Dermatology and Venereology) Congress, Paris, France, 12-16 September 2018.
Andreia Feital da Costa Pereira, Renan Lage, Mamy Honda Igarashi, Sheila Gomes da Silva, Maurizio Mercuri, Elis Angela de Alcantara Viana, Lucia de Fatia Holanda Paiva de Araújo, Amanda Francielli Pereira, Suelma Natalie de Melo Oliveira, Michelle Sabrina Silva, Gustavo Facchini, Ana Lúcia Alves Tabarini Pinheiro, Samara Eberlin.

Atopic dermatitis (AD) is a chronic, recurrent, and inflammatory skin disease, characterized by the presence of eczematous lesions and pruritus. Despite the large number of clinical and experimental studies, and subsequent advances in this field, the pathophysiology of AD remains unclear. The most recent hypotheses about the pathogenesis of AD involve numerous factors: genetic predisposition, environmental factors, altered immune function, and skin barrier dysfunction. Innate and adaptive immunity has a definitive role in the development, maintenance, and crisis of AD. This process involves a complex interaction between T cells, antimicrobial peptides, cytokines, and keratinocytes. The alteration in the balance of the immune system directly influences the rupture of the skin barrier, characteristic of AD lesions, making individuals predisposed to skin infections. In the present study, we evaluated the preclinical efficacy of an active complex (AC) in anti-inflammatory response in cultures of human monocytes/macrophages (THP-1) stimulated with lipoteichoic acid (LTA) to induce the inflammatory microenvironment. Additionally, we evaluated the preclinical efficacy of a moisturizing formulation containing the AC (Hydra-AI) in the synthesis of filaggrin, involucrin, and loricrin in ex vivo skin fragments submitted to epidermal barrier rupture. Cultures of THP-1 were differentiated into phagocytes with 12-myristate 13-acetate phorbol. Afterward, the cultures were stimulated with LTA (10 μM) to induce the inflammatory microenvironment and treated with AC at 0.100, 0.0316, and 0.0100 mg/ml. Cell lysates and culture supernatants were collected for quantification of interleukins 4, 10, 13, 17, 31, and NF-κB using the ELISA technique. In parallel, ex vivo skin fragments were treated with Hydra-AI for two consecutive days, with a 24-hour interval between each application. The epidermis was ruptured using 4% sodium lauryl sulfate (SDS), and after 24 hours, the fragments were treated again with Hydra-AI. Fragments were collected, fixed, and cryopreserved for evaluation by immunofluorescence of filaggrin, involucrin, and loricrin. The results obtained demonstrated that the treatment with AC performed on the LTA-stimulated THP-1 cell cultures was able to significantly reduce the inflammatory mediators IL-4, 10, 13, 17, 31, and the signaling pathway NF-κB when compared to the stimulated group. In addition, immunofluorescence evaluations demonstrated that HYDRA-AI stimulates the synthesis of filaggrin, involucrin, and loricrin in fragments of ex vivo skin submitted to rupture of the epidermal barrier with SDS. The results obtained allow us to infer that AC presents anti-inflammatory activity, reducing the exacerbated production of mediators associated with the development of AD, which contribute to the impairment of the cutaneous barrier. In addition, HYDRA-AI upregulates the synthesis of filaggrin, loricrin, and involucrin, suggesting a positive effect on skin barrier protection, hydration, proliferation, differentiation, epidermal cohesion, and synthesis of NMF. Taken together, these results demonstrate that AC and the moisturizing formulation containing AC (HYDRA-AI) have a protective and restorative effect on sensitive skin, associated with atopic dermatitis.