title: Serum levels of tumor necrosis factor-alpha, interleukin-1, and interferon-gamma in beta(o)-thalassemia/HbE and their clinical significance.
abstract: Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), and interferon-gamma (IFN-gamma) were estimated by conventional ELISA kits in 60, 42, and 58 Thai patients, respectively, with beta(o)-thalassemia HbE and found to be above the normal range in 13%, 21%, and 33% of the patients, respectively. Using high-sensitivity ELISA systems, an additional 10 beta(o)-thal/HbE patients were compared with 9 controls for concentrations of circulating TNF-alpha and IL-1beta, and 9 and 5 patients, respectively, but only 1 and none of the controls, respectively, showed values above the normal ranges. In patients with abnormally high IFN-gamma levels, basal hemoglobin values were significantly lower than in those with normal levels of the cytokine (mean +/- SEM: 6.03+/-0.24 vs. 7.08+/-0.18, p < 0.05), although circulating concentrations of soluble transferrin receptors (sTrF) and absolute reticulocyte counts were similar in the two groups. Patients with raised or normal levels of TNF-alpha, IL-1alpha, or IL-1beta had similar basal hemoglobin values. In a phagocytosis assay, monocytes of patients with raised serum levels of IFN-gamma showed significantly more attached or ingested IgG-coated red cells than those of patients with normal concentrations of the cytokine (mean +/- SEM: 192+/-22 vs. 140+/-14 per 100 monocytes, p < 0.05). Moreover, in 3 of 4 of the former patients, the number of attached or ingested IgG-coated red cells per 100 monocytes was above the 95% reference limit for the latter patients. The results suggest that IFN-gamma aggravates the anemia of beta(o)-thal/HbE by activating mononuclear phagocytes for destruction of red cells but not by inhibiting erythropoiesis. The elevated serum levels of TNF-alpha and IL-1 could contribute to complications of the disease, such as cachexia and thromboembolic phenomena.
authors: Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. siwwn@mahidol.ac.th
authors: W
authors: W
authors: Wanachiwanawin
authors: E
authors: E
authors: Wiener
authors: U
authors: U
authors: Siripanyaphinyo
authors: S
authors: S
authors: Chinprasertsuk
authors: F
authors: F
authors: Mawas
authors: S
authors: S
authors: Fucharoen
authors: S N
authors: SN
authors: Wickramasinghe
authors: P
authors: P
authors: Pootrakul
authors: S
authors: S
authors: Visudhiphan
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006402:Hematologic Diseases / Q000097:blood; D006446:Hemoglobin E / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D007375:Interleukin-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010586:Phagocytes / Q000378:metabolism; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D017086:beta-Thalassemia / Q000097:blood*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D006446:Hemoglobin E