Blunted erythropoietin response to anaemia in tuberculosis.
The precise cause of the anaemia that is commonly associated with severe pulmonary tuberculosis (PTB) has not been elucidated. The role of erythropoietin (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 matched individuals with uncomplicated iron deficiency; group 4, healthy volunteers. Peripheral blood monocytes were obtained from patients with PTB and the controls, cultured, and the supernatant fluid (SNF) harvested. Tumour necrosis factor alpha (TNF alpha) levels were determined in the SNF, which were then added in various dilutions to a hepatocellular carcinoma cell line (HepG2) capable of regulated EPO synthesis in vitro. The influence of this cytokine was defined by the addition of specific neutralising anti-TNF alpha antibodies in this assay system. Patients in group 1 had significantly lower Epo levels (54 + 11 mU/mL) compared with those in group 3 (142 +/- 41 mU/mL) (p < 0.01). Monocyte supernatants from patients in the anaemic PTB group had markedly elevated TNF alpha levels and significantly suppressed Epo output by HepG2 cells in vitro (p < 0.01). This inhibition was consistently abrogated by anti-TNF alpha antibodies. Serum Epo levels were inappropriately low in untreated PTB patients when compared with corresponding haemoglobin levels in iron deficient controls. This blunted response could be ascribed to release of TNF alpha or other cytokines by activated monocytes.
Ebrahim
O
O
Department of Pharmacology, University of Cape Town Leukaemia Centre, South Africa.
Folb
P I
PI
Robson
S C
SC
Jacobs
P
P
D000740:Anemia / Q000097:blood* / Q000209:etiology; D001681:Biological Assay; D006528:Carcinoma, Hepatocellular; D002478:Cells, Cultured; D004921:Erythropoietin / Q000097:blood*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008113:Liver Neoplasms; D008214:Lymphocytes / Q000276:immunology; D012016:Reference Values; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000150:complications*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D006454:Hemoglobins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin