1. Serum levels of erythropoietin and the immune parameters tumour necrosis factor-α, soluble interleukin-2 receptor, interleukin-2, interleukin-6 and interferon-γ were measured in patients with rheumatoid arthritis.
2. Out of 69 patients, 44 had anaemia with serum haemoglobin concentrations of 10.8 (SD 1.2) g/dl. In these patients erythropoietin levels were significantly higher than in non-anaemic patients [51.97 (SD 23.9) versus 26.06 (SD 11.9) m-units/ml; P < 0.0001; control patients: 18.1 (SD 13.8) m-units/ml]. Mean soluble interleukin-2 receptor activity was elevated in all patients with rheumatoid arthritis [1324 (SD 715) units/ml; control patients: 480 (SD 75) units/ml; P < 0.001] and was significantly higher in the anaemic group than in the non-anaemic group [1562 (SD 662) versus 696 (SD 402) units/ml; P < 0.0001]. The serum activity of soluble interleukin-2 receptor showed an inverse correlation with haemoglobin (r = 0.79; P < 0.0001) and a positive correlation with erythropoietin (r = 0.70, P < 0.0001).
3. Elevated serum tumour necrosis factor-α levels were found in 19 anaemic patients [20.6 (SD 9.1) pg/ml]. Concentrations of tumour necrosis factor-α in serum showed an inverse correlation with haemoglobin (r = 0.57, P < 0.001) and a positive correlation with erythropoietin (r = 0.46, P < 0.05). Interleukin-6 was detected in seven anaemic patients [21 (SD 14) pg/ml] and interleukin-2 activity in three anaemic patients (12, 16 and 14 units/ml, respectively). Interferon-γ was not detected in any of the patients investigated.
4. The present study supports the concept that in patients with rheumatoid arthritis the responsiveness to erythropoietin is impaired. Immune mechanisms may be operative and point to a pivotal role for tumour necrosis factor-α.