Interleukin-1, Tumor Necrosis Factor-Alpha and Interferon Gamma in Hepatic Schistosomiasis: Relation to Erythropoiesis.
Nabil A. El-Halawani1, Hoda A. El-Aggan2, Myriam Abou Seif 3 and Sawsan M. Bakhubira1.
Departments of Medicine (Hematology1 and Hepatobiliary2 Units) and Clinical Pathology3, Faculty of Medicine, Alexandria University, Egypt.

Hepatic schistosomiasis is an immunoregulatory disease characterized by elaboration of various cytokines and is frequently associated with anemia. Therefore, the present study was designed to determine the inter-relationship between serum interleukin-1 (IL-1), tumor necrosis factor- alpha (TNF-a) and interferon gamma (IFN-g) and erythropoiesis in this disease. Thirty eight patients with schistosomal hepatic fibrosis (SHF) and well- compensated liver disease (23 were anemic and 15 were non-anemic), were included in the study as well as 12 healthy subjects as a control group. Active schistosomiasis was found in 26 patients. Serum levels of IL- 1b, TNF-a and IFN-g were measured using immunoenzymatic assay. Bone marrow (BM) was examined for cytological study and by Prussian blue stain to detect iron granules. Parameters of serum iron status (serum iron, total iron binding capacity, transferrin saturation and serum ferritin) were also measured. In patients with SHF, serum levels of IL-1B, TNF-a and IFN-g were significantly elevated unrelated to disease activity. Bone marrow examination in these patients showed erythroid hyperplasia with late erythroid maturation arrest regardless of the presense of anemia. Using Prussian blue stain, only patients with anemia had reduced sideroblast percentage associated with hypoferremia and low transferrin saturation. However, despite these changes, BM iron stores and serum ferritin levels were normal (functional iron deficiency) in 10 (43.5%) patients with anemia simulating the picture of "anemia of chronic disease" and were below normal in the other anemic patients suggesting the coexistence of true iron deficiency. Of the studied cytokines, only TNF-a serum levels were significantly higher in anemic than in non-anemic patients. This cytokine showed a direct relationship with the degree of late erythroid maturation arrest and inverse correlations with serum iron levels, transferrin saturations, sideroblast percentages and hemoglobin crationcentons in patients with SHF. It is concluded that elevation of serum levels of IL-1b, TNF-a and IFN-g occurs in hepatic schistosomiasis unrelated to disease activity. Of these cytokines, TNF-a seems to play an important role in the suppression of late erythropoiesis, disturbance in iron metabolism and development of anemia in this disease. Therefore, the immune-mediated mechanism has to be considered in the management of anemia in patients with hepatic schistosomiasis.

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