{Reference Type}: Journal Article {Title}: Local and Systemic Inflammation in Finnish Dairy Cows with Digital Dermatitis. {Author}: Pirkkalainen H;Riihimäki A;Lienemann T;Anttila M;Kujala-Wirth M;Rajala-Schultz P;Simojoki H;Soveri T;Orro T; {Journal}: Animals (Basel) {Volume}: 14 {Issue}: 3 {Year}: 2024 Jan 31 {Factor}: 3.231 {DOI}: 10.3390/ani14030461 {Abstract}: Digital dermatitis is a disease of the digital skin and causes lameness and welfare problems in dairy cattle. This study assessed the local and systemic inflammatory responses of cows with different digital dermatitis lesions and compared macroscopical and histological findings. Cow feet (n = 104) were evaluated macroscopically and skin biopsies histologically. Serum samples were analyzed for acute phase proteins (serum amyloid A and haptoglobin) and pro-inflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha). Cows with macroscopically graded active lesions (p = 0.028) and non-active lesions (p = 0.008) had higher interleukin-1 beta levels in their serum compared to healthy cows. Interleukin-1 beta serum concentrations were also higher (p = 0.042) when comparing lesions with necrosis to lesions without necrosis. There was no difference when other cytokine or acute phase protein concentrations in healthy cows were compared to those in cows with different digital dermatitis lesions. A novel histopathological grading was developed based on the chronicity of the lesions and presence of necrosis and ulceration. The presence and number of spirochetes were graded separately. In the most severe chronic lesions, there was marked epidermal hyperplasia and hyperkeratosis with necrosis, deep ulceration, and suppurative inflammation. Spirochetes were found only in samples from necrotic lesions. This study established that digital dermatitis activates proinflammatory cytokines. However, this did not initiate the release of acute phase proteins from the liver. A histopathological grading that takes into account the age and severity of the lesions and presence of spirochetes was developed to better understand the progression of the disease. It is proposed that necrosis of the skin is a result of ischemic necrosis following reduced blood flow in the dermal papillae due to pressure and shear stress caused by thickened epidermis, and that the spirochetes are secondary invaders following tissue necrosis.