Elevated levels of inflammatory cytokines in bone marrow of patients with rheumatoid arthritis and anemia of chronic disease.
OBJECTIVE
Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) play an important role in decreased erythropoiesis in patients with anemia of chronic disease (ACD) and rheumatoid arthritis (RA). Modulation of quantities of bone marrow erythroid progenitors during chronic inflammation may be one of the pathogenetic mechanisms leading to ACD. We studied bone marrow from patients with ACD with RA by investigating, first, local production of inflammatory cytokines in the bone marrow, and second, the relative fraction of late erythroid progenitors (erythropoietin and transferrin receptor positive cells; EpoR+ TrfR+) in bone marrow. In addition, the effects of TNF-alpha on EpoR+ TrfR+ cells were studied in vitro.


METHODS
Levels of IL-6 and TNF-alpha were measured by EL ELISA in supernatant of bone marrow and peripheral blood cultures from 14 patients with RA and ACD and 14 patients with RA without anemia. The numbers of EpoR+ TrfR+ cells in bone marrow samples of both groups were assessed by 2 color fluorescence flow cytometry.


RESULTS
Levels of IL-6 and TNF-alpha were significantly higher in the supernatant of bone marrow cultures of patients with ACD compared to controls. No significant differences in the fraction of EpoR+ TrfR+ cells in samples was observed between the 2 groups of patients. Incubation of the samples with TNF-alpha did not result in modulation of the number of EpoR+ TrfR+ cells.


CONCLUSIONS
Local production of proinflammatory cytokines in the bone marrow may be associated with the development of ACD in RA.
Jongen-Lavrencic
M
M
Department of Rheumatology, Dr. Daniel den Hoed Clinic, Rotterdam, The Netherlands.
Peeters
H R
HR
Wognum
A
A
Vreugdenhil
G
G
Breedveld
F C
FC
Swaak
A J
AJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D004900:Erythroblasts / Q000378:metabolism*; D004921:Erythropoietin / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D015850:Interleukin-6; D011990:Receptors, Transferrin; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin