ACTIVATION OF CD4(-LYMPHOCYTES IN BONE-MARROW ASSOCIATED WITH REDUCEDERYTHROPOIESIS IN PATIENTS WITH CHRONIC INFLAMMATION AND ANEMIA() ANDCD8(+) T)

We hypothesised that, in ''anaemia of chronic disorders'' (ACD), a loc al immune activation in the bone marrow alters erythropoiesis. We dete rmined the activation status of bone marrow T-lymphocytes and the leve ls of cytokines. Patients (n = 27) with chronic inflammatory diseases and low hemoglobin values who had undergone bone marrow aspiration wer e divided into 2 groups according to the aetiology of anaemia: (1) unk nown or (2) known causes (i.e. iron, folic acid and/or vitamin Bit def iciencies). Cytokines in peripheral blood and bone marrow serum were m easured by ELISA and T-lymphocytes were phenotyped by flow cytometry. Peripheral blood from 27 age-matched healthy donors and bone marrow fr om 3 transplantation donors served as control. The erythrocyte count i n the peripheral blood of patients with unknown aetiology of anaemia ( group 1) was lower than in patients with known aetiology (group 2). Th is indicated that group 1 included most patients with ACD. Both groups had active disease, as shown by elevated levels of C-reactive protein and the erythrocyte sedimentation rate. The levels of IL-6 and IL-7 i n the peripheral blood were higher in patients of group 1 than in pati ents of group 2 or normal subjects. The levels of IL-6, IL-7 and TNF-a in the bone marrow also were higher in group 1 compared to group 2. T he CD4(+) and CD8(+) T-lymphocytes of the bone marrow showed a more ac tivated phenotype than peripheral blood T-lymphocyte with the number o f T-lymphocytes that expressed the early activation marker, CD69, bein g higher in group 1 than in group 2. A smaller proportion of ''naive'' cells (CD45RO(-), CD69(-)) was accompanied by a higher proportion of ''false naive'' cells (CD45RO(-), CD69(+)). In the bone marrow, elevat ed levels of IL-7 were correlated with fewer ''naive'' and more ''fals e naive'' cells in the CD4(+) T-lymphocyte subpopulation. In group 1 o nly, a significant inverse relation was observed between the erythrocy te counts in blood and the levels of IL-7 in bone marrow. Thus, in pat ients with unknown aetiology of anaemia - a group including most patie nts with ACD-, an interrelationship may exist between the local activa tion of bone marrow T-lymphocytes, increased production of cytokines, and reduced erythropoiesis.