Analysis of Systemic and Cutaneous Inflammatory Immune Response in Canine Atopic Dermatitis

Abstract

Background: Canine atopic dermatitis (CAD) is a chronic and inflammatory disease present in veterinary dermatological practice. The inflammation in CAD is triggered by environmental allergens and skin microorganisms, which are responsible for the worsening of cutaneous lesions. This continuous activation of skin inflammatory process can induce the production of free radicals that also contribute to cellular damage and ultimately leads to changes in blood parameters in dogs with CAD. Although there are reports of inflammatory parameters in CAD, there are a lack of studies correlating skin lesions, blood leukocytes and oxidative stress. Based on that,this study aimed to evaluate the integumentary and systemic inflammatory response in dogs with atopic dermatitis. Materials, Methods & Results: Dogs with confirmed diagnosis of canine atopic dermatitis (n = 10) were divided in two groups according to CADESI-IV: AI, with CADESI between 0-10, AII, with CADESI between 10-34, and control group (n = 5). Blood-biochemical and histological analysis were performed to access systemic and cutaneous inflammatory response. AII group tended to higher neutrophil and eosinophil counts, as well as neutrophil/lymphocyte ratio (NLR) when compared to AI. The albumin was lower in AII compared to AI and control (P < 0.05), while total bilirubin and malondialdehyde (MDA) did not differ between groups. NLR (r = 0.64 and P = 0.04) and MDA (r = 0.54 and P = 0.1) were positively correlated with CADESI, while albumin was negatively correlated with CADESI (r = -0.79 and P = 0.005). Histopathological analysis revealed a larger number of neutrophils, macrophages and mast cells in AI and AII than in control group (P < 0.05). Discussion: In this study it was possible to evaluate the systemic and cutaneous leukocyte dynamics in CAD. Skin inflammation induces the production of chemotactic molecules contribute to neutrophil outflow from blood vessel toward the affected tissue, which can be visualized as perivascular inflammatory infiltrate and exocytosis. At systemic level, there was a tendency to increase in total leukocytes and circulating neutrophil count in group AII, as well as in neutrophil/lymphocyte ratio (NLR), when compared to AI. The NLR is a widely available and inexpensive laboratory biomarker that quantifies systemic inflammation, being used in human medicine to evaluate prognosis in different types of cancer. In our study, dogs in AII group showed an increased NLR compared to AI and control, which demonstrates the influence of skin injury in systemic parameters. Furthermore, AII group is composed of dogs with greater lesion state, which reflects in higher NLR values. Since this disease is known by its chronicity and may remain stable for years, NLR may be a novel biomarker to evaluate acute exacerbation in CAD and could potentially explain why some patients have longer crisis duration and frequent flares. The maintenance of the inflammatory state also induces the production of oxidizing substances, which possibly exceed the total antioxidant capacity, generating a situation of oxidative stress, which can result in damage to membrane lipids and release of their products. MDA is reliable and is the most commonly used marker of the overall lipid peroxidation level and the presence of oxidative stress. This result may be related with the antioxidant system, such as albumin and bilirubin, which was able to promote an efficient control of oxidant substances. In conclusion, the presented data demonstrated an inflammatory process progression as well as introduced NLR as a potential marker of disease exacerbation in CAD.