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Introduction Lumpy skin disease (LSD) is a transboundary viral disease of cattle caused by the lumpy skin disease virus (LSDV), leading to significant economic losses in livestock. Materials The present study investigated the clinical, hematological, and pathological alterations and expression of cytokine genes in cattle naturally affected by LSD. A total of 21 clinically affected individuals were examined and classified into early, mid, and late stages. The study focused on key diagnosis of LSD by clinical findings, hematology, indirect ELISA, histopathology, immunohistochemistry, PCR, and the relative expression of cytokine genes associated with both proinflammatory (IL-2, IFN-g, and GM-CSF) and anti-inflammatory (IL-4, and IL-10) responses using real-time PCR. Results Affected animals exhibited stage-dependent clinical signs. Hematological analysis revealed a significant increase in total leukocyte count (TLC) and absolute lymphocyte count (ALC) in late-stage LSD cases, reflecting an active inflammatory response. PCR detected LSDV DNA in 52.4% of nasal swabs and 57.1% of skin biopsy samples. The cytokine gene expression analysis showed a downregulation of IL-2, IL-4, IL-10, IFN-g, and GM-CSF in both peripheral blood mononuclear cells (PBMCs) and skin tissue samples from LSD-affected cattle, suggesting an impaired immune response. Discussion This reduced expression likely contributes to the persistence of LSDV in affected cattle, leading to prolonged inflammation and increased susceptibility to secondary infections. In contrast, healthy cattle exhibited a stronger Th1 cell response, indicating better immune regulation and disease resilience. The findings highlight the role of immune dysregulation in the progression of LSD and suggest that cytokine modulation by LSDV is a key mechanism for immune evasion.
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