Mechanism of anaemia in rheumatoid arthritis: demonstration of raised interleukin 1 beta concentrations in anaemic patients and of interleukin 1 mediated suppression of normal erythropoiesis and proliferation of human erythroleukaemia (HEL) cells in vitro.

Abstract

SUMMARY The pathogenesis of the anaemia associated with rheumatoid disease is unclear. It has previously been shown that the degree of the anaemia correlates with the severity of the inflammatory disease and that serum from patients with arthritis inhibits erythropoiesis. This study was designed to examine whether interleukin 1 could be a mediator of the anaemia in rheumatoid arthritis. Radioimmunoassay of interleukin 1 in serum showed that patients with rheumatoid arthritis and associated anaemia had significantly higher interleukin 13 concentrations than patients with rheumatoid arthritis without anaemia. Pure recombinant human interleukin la and interleukin 113, in concentration ranges similar to those found in the arthritic patients, markedly suppressed the colony formation of the erythroid, but not the granulocyte-macrophage progenitor cells in cultures of normal bone marrow. Natural human interleukin 1 and recombinant interleukin 113, but not interleukin la, suppressed in a dose dependent manner the proliferation of the human erythroleukaemia cell line (HEL) in cultures, suggesting that the interleukin 1 effect is a direct one. The results show that interleukin 1 is a humoral inhibitor of erythropoiesis and suggests that interleukin 1 is involved in the development of anaemia in association with rheumatoid arthritis.

Late stage erythroid precursor production is impaired in mice with chronic inflammation

“…35,36 Individual cytokines, such as IL-6, have also been correlated with the severity of the anemia in chronic disease states. [37][38][39] Colony-forming assays are robust assays of proliferative capacity, but they are not well suited for the analysis of the later stages of erythroid maturation. Late stages of erythroid maturation proceed independently of erythropoietin and after the majority of cell divisions have occurred.…”

Regulation of hepcidin transcription by interleukin-1 and interleukin-6

“…Moreover, the addition of anti-IL-6 antibody did not ablate the IL-1 effect. IL-1 induces hypoferremia (17), up-regulates ferritin (18), and has been thought to play a primary role in the anemia of chronic inf lammation (8). It may well be that it is stimulation of hepcidin by IL-1 that plays a more important role in the anemia of inf lammation than does IL-6.…”

Anemia and Periodontitis: An Enigma?

“…17 Johnson et al 18 exposed mice to a single intravenous dose of TNF-a,which resulted in suppression of spleen and marrow erythroid colony-forming units. Johnson et al 18 treated mice with single or repeated intraperitoneal injections of recombinant human IL-1a, which resulted in suppression of mature erythroid progenitors within 6 hours.Maury et al 19 reported that recombinant human IL-1 (a and b) inhibited in vitro colony formation by erythroid burst-forming units and erythroid colony forming units from normal human marrow. In vitro colony formation by marrow granulocyte-macrophage progenitors was not inhibited by IL-1a.…”