Activation of CD4+ and CD8+ T-lymphocytes in bone marrow associated with reduced erythropoiesis in patients with chronic inflammation and anaemia.
We hypothesised that, in "anaemia of chronic disorders" (ACD), a local immune activation in the bone marrow alters erythropoiesis. We determined the activation status of bone marrow T-lymphocytes and the levels of cytokines. Patients (n = 27) with chronic inflammatory diseases and low hemoglobin values who had undergone bone marrow aspiration were divided into 2 groups according to the aetiology of anaemia: (1) unknown or (2) known causes (i.e. iron, folic acid and/or vitamin B12 deficiencies). Cytokines in peripheral blood and bone marrow serum were measured by ELISA and T-lymphocytes were phenotyped by flow cytometry. Peripheral blood from 27 age-matched healthy donors and bone marrow from 3 transplantation donors served as control. The erythrocyte count in the peripheral blood of patients with unknown aetiology of anaemia (group 1) was lower than in patients with known aetiology (group 2). This 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 in the peripheral blood were higher in patients of group 1 than in patients of group 2 or normal subjects. The levels of IL-6, IL-7 and TNF-alpha in the bone marrow also were higher in group 1 compared to group 2. The CD4+ and CD8+ T-lymphocytes of the bone marrow showed a more activated phenotype than peripheral blood T-lymphocyte with the number of T-lymphocytes that expressed the early activation marker, CD69, being 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, elevated levels of IL-7 were correlated with fewer "naive" and more "false naive" cells in the CD4+ T-lymphocyte subpopulation. In group 1 only, a significant inverse relation was observed between the erythrocyte counts in blood and the levels of IL-7 in bone marrow. Thus, in patients with unknown aetiology of anaemia--a group including most patients with ACD-, an interrelationship may exist between the local activation of bone marrow T-lymphocytes, increased production of cytokines, and reduced erythropoiesis.
Neidhart
M
M
Department of Rheumatology and Physical Medicine, University Hospital Zurich.
Brühlmann
P
P
Gay
S
S
Michel
B A
BA
D000328:Adult; D000368:Aged; D000740:Anemia / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D004920:Erythropoiesis / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000175:diagnosis / Q000276:immunology*
D016207:Cytokines