Mitogen-induced stimulation and suppression of erythroid burst promoting activity production by human mononuclear cells

Exposure of human peripheral blood mononuclear cells or highly enriched monocytes to various plant lectins substantially alters their production of erythroid burst promoting activity (BPA). Neither unstimulated, nor mitogen stimulated, enriched T lymphocytes produced demonstrable BPA. Each of the lectins tested resulted in a different pattern of alteration of BPA production by mononuclear cells. Increasing concentrations of phytohaemagglutinin (PHA) caused a progressive increase in BPA production up to a plateau level at concentrations above 0·25–0·5 Μ1/ml. Concanavalin A (Con A) at concentrations of 0·05–0·1 Μg/ml stimulated BPA production, but Con A concentrations > 1 Μg/ml never augmented BPA production by mononuclear cells. Pokeweed mitogen inhibited BPA production by mononuclear cells in a concentration-dependent manner. Since PHA and Con A can bind to and stimulate both monocytes/macrophages and T lymphocytes, some production of BPA by stimulated T cells in the presence of monocytes cannot be ruled out. Earlier studies demonstrated that T cells augment monocyte production of BPA. Thus, monocyte–T cell interactions, as well as activation of monocytes and perhaps lymphocytes, play an important role in regulation of BPA production in vitro .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73808/1/j.1365-2141.1983.tb01232.x.pd

Interaction of inflammatory cytokines and erythropoeitin in iron metabolism and erythropoiesis in anaemia of chronic disease

In chronic inflammatory conditions increased endogenous release of specific cytokines (TNFα, IL-1, IL-6, IFNγ and others) is presumed. It has been shown that those of monocyte lineage play a key role in cytokine expression and synthesis. This may be associated with changes in iron metabolism and impaired erythropoiesis and may lead to development of anaemia in patients with rheumatoid arthritis. Firstly, increased synthesis of acute phase proteins, like ferritin, during chronic inflammation is proposed as the way by which the toxic effect of iron and thereby the synthesis of free oxy-radicals causing the damage on the affected joints, may be reduced. This is associated with a shift of iron towards the mononuclear phagocyte system which may participate in the development of anaemia of chronic disease. Secondly, an inhibitory action of inflammatory cytokines (TNFα, IL-1), on proliferation and differentiation of erythroid progenitors as well as on synthesis of erythropoietin has been shown, thereby also contributing to anaemia. Finally, chronic inflammation causes multiple, complex disturbances in the delicate physiologic equilibrium of interaction between cytokines and cells (erythroid progenitors, cells of mononuclear phagocyte system and erythropoietin producing cells) leading to development of anaemia of chronic disease (Fig. 1)

A simplified endogenous erythroid colony assay for the investigation of polycythaemia

The in vitro growth of erythroid colonies in the absence of erythropoietin, known as endogenous erythroid colonies (EEC) forms part of the diagnostic criteria for polycythaemia vera (PV). The availability of EEC culture in routine laboratory setting is limited as culture methods are technically demanding, difficult to standardize, expensive and laborious. In this study, we assessed the performance characteristics of a simplified method using ammonium chloride red cell lysis followed by culture on commercially available, batch-tested, methylcellulose media. Seventy-six patients were included; four were secondarily excluded on the basis of culture failure. Of the 14 patients with PV, 13 (93%) were positive for EEC on at least one occasion: 90% (nine of 10) of bone marrow and 67% (six of nine) of peripheral blood specimens were positive. All 30 patients with secondary polycythaemia (n = 12) or apparent polycythaemia (n = 18) were negative for EEC. The incidence of EEC in idiopathic erythrocytosis was 40% (eight of 28); 50% (five of 10) in those who met one of the minor criteria for PV and 17% (three of 18) in those who did not. We conclude that our EEC assay yield results comparable with that of more elaborate methods