Histopathological and Immunobiochemical Alterations Associated with Natural Fasciola hepatica Infection in Sheep: Emphasis on IL-10–Mediated Immune Modulation

Abstract

Background: Fasciolosis is a significant helminthic disease of sheep, affecting the liver and bile ducts, and causing economic losses. Fasciola hepatica has been demonstrated to induce a regulatory immune response in the host, with an important role for the cytokine interleukin-10 (IL-10). The primary objective of this study was to characterise the histopathological, haematological, biochemical and immunological changes in natural infected sheep infected with F. hepatica, focusing on the level of IL-10 in the serum and its correlation with hepatobiliary damage. Thirty local breed sheep (1-3 years old) were examined in Samarra Municipal Abattoir, Salah Al-din Province, Iraq, from November 2025 to February 2026 and were divided into naturally infected group (n=15) and healthy control group (n=15). Diagnosis of infection was made by faecal sedimentation and Ure 1988's recovery of adult flukes from the bile ducts. Haemoglobin (Hb), liver enzymes (AST, ALT, ALP, GGT) and serum IL-10 (ELISA) were analyzed and liver tissue was assessed by H&E and Masson's trichrome staining. Student's t-test and Pearson's correlation were used to analyse data. Results: The level of Hb was significantly reduced in the infected group (8.74 ± 0.63 g/dL vs 12.49 ± 0.39 g/dL) and all liver enzymes were significantly elevated in the infected sheep (P < 0.001), with the greatest increases observed for the cholangiocellular markers GGT (+143%) and ALP (+102%). Serum IL-10 was markedly elevated in infected animals (46.20 ± 5.37 vs. 19.13 ± 1.85 pg/mL; P < 0.001) and correlated very strongly with GGT (r = 0.994), ALP and ALT (r = 0.983), and AST (r = 0.964), and inversely with Hb (r = −0.616). Histopathology confirmed eosinophilic infiltrates around the portal areas, hyperplasia of the bile ducts, cholangitis and significant fibrosis. In conclusion, natural infection of sheep with F. hepatica causes predominantly cholangiocellular liver damage in sheep, which is accompanied by an IL-10-driven immunomodulatory response and anaemia. The hepatobiliary damage in both IL-10 and disease severity is well correlated, indicating that both processes are tightly coupled with infection intensity, and thus, the usefulness of IL-10 as an auxiliary marker of disease severity in ovine fasciolosis. It is important to note that due to the small sample size and correlational design, these results are preliminary.