Serum levels of tumor necrosis factor-alpha, interleukin-1, and interferon-gamma in beta degrees-thalassemia/HbE and their clinical significance

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alph a (IL-1 alpha), and interferon-gamma (IFN-gamma) were estimated by conventi onal ELISA kits in 60, 42, and 58 Thai patients, respectively, with beta de grees-thalassemia HbE and found to be above the normal range in 13%, 21%, a nd 33% of the patients, respectively. Using high-sensitivity ELISA systems, an additional 10 beta degrees-thal/HbE patients were compared with 9 contr ols for concentrations of circulating TNF-alpha and IL-1 beta, 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 tho se 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 transf errin receptors (sTrF) and absolute reticulocyte counts were similar in the two groups. Patients with raised or normal levels of TNF-alpha, IL-1 alpha , or IL-1 beta had similar basal hemoglobin values. In a phagocytosis assay , monocytes of patients with raised serum levels of IFN-gamma showed signif icantly more attached or ingested IgG-coated red cells than those of patien ts with normal concentrations of the cytokine (mean +/- SEM: 192 +/- 22 us. 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 re sults suggest that IFN-gamma aggravates the anemia of beta degrees-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 t hromboembolic phenomena.