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.