BLUNTED ERYTHROPOIETIN RESPONSE TO ANEMIA IN TUBERCULOSIS

The precise cause of the anaemia that is commonly associated with seve re pulmonary tuberculosis (PTB) has not been elucidated. The role of e rythropoietin (Epo), the central hormone regulating red cell formation , still awaits clarification. We therefore determined serum Epo levels in patients with PTB; group 1, haemoglobin less than 110 g/L, group 2 , haemoglobin greater than 110 g/L; group 3, controls, consisted of ma tched individuals with uncomplicated iron deficiency; group 4, healthy volunteers. Peripheral blood monocytes were obtained from patients wi th PTB and the controls, cultured, and the supernatant fluid (SNF) har vested. Tumour necrosis factor alpha (TNF alpha) levels were determine d in the SNF, which were then added in various dilutions to a hepatoce llular carcinoma cell line (HepG2) capable of regulated EPO synthesis ill vitro. The influence of this cytokine was defined by the addition of specific neutralising anti-TNF alpha antibodies in this assay syste m. Patients in group 1 had significantly lower Epo levels (54 +/- 11 m U/mL) compared with those in group 3 (142 +/- 41 mU/mL) (p < 0.01). Mo nocyte supernatants from patients in the anaemic PTB group had markedl y elevated TNF alpha levels and significantly suppressed Epo output by HepG2 cells in vitro (p < 0.01). This inhibition was consistently abr ogated by anti-TNF alpha antibodies. Serum Epo levels were inappropria tely low in untreated PTB patients when compared with corresponding ha emoglobin levels in iron deficient controls. This blunted response cou ld be ascribed to release of TNF alpha or other cytokines by activated monocytes.