IL-7 deficiency in rheumatoid arthritis (RA). (a) IL-7 levels were measured in serum from 34 healthy control individuals (median age 46 years), 28 patients with RA (seven with recent onset RA before institution of therapy and 21 with established, refractory RA; median age 55 years) and 12 patients with established osteoarthritis (OA; median age 56 years). Control individuals had significantly higher levels of circulating IL-7 than did RA patients (P < 0.00001). OA patients tended to have lower IL-7 levels than healthy control individuals (P = 0.035) but higher than RA patients (P < 0.00001). (b) IL-7 levels were plotted against C-reactive protein (CRP) values for 28 patients with active RA, but no relationship could be identified (R = 0.201, P = 0.161). (c) Bone marrow was obtained by aspiration from the iliac crest from healthy control individuals (n = 15) and from RA patients (n = 8) before and after therapeutic tumour necrosis factor (TNF)-α blockade. Long-term bone marrow stromal cell cultures were established, and spontaneous IL-7 release was measured. Control bone marrow stromal cells released significantly more IL-7 than did RA marrow (P = 0.001). There was no consistent effect of anti-TNF-α therapy on IL-7 expression (paired pre-post treatment test). (d) Peripheral blood mononuclear cells from healthy control individuals (n = 3) and RA patients (n = 3) were cultured in the presence of PHA (10 μg/ml), IL2 (20 U/ml), anti-CD3 (1 μg/ml) plus anti-CD28 (5 μg/ml), or titrated doses of IL-7 (1–100 ng/ml), for 5 days. Proliferation was assayed by 3H-thymidine incorporation. RA and healthy cells responded similarly to IL-7, but RA cells were hyporesponsive to other stimuli.