Soluble Apoptotic Biomarkers, Lipocalin-2, Proinflammatory Cytokines, and Reticulocyte Maturity Index in Anemia of...

Anemia of inflammation is common in patients with infections, autoimmune diseases, chronic inflammation, and various cancers. Few studies have investigated the effects of apoptosis, lipocalin-2, and cytokines on erythropoiesis in anemia of inflammation. This study explored the relationship between serum-soluble apoptotic biomarkers, lipocalin-2, erythropoietin, inflammatory cytokines, and reticulocyte production in anemia of inflammation.

A total of 164 patients with systemic inflammation were evaluated. Levels of APO-1, lipocalin-2, erythropoietin, tumor necrosis factor (TNF)-α, TNF-related apoptosis-inducing ligand (TRAIL), and interleukin (IL)-6 were measured. To assess erythropoietic activity, the reticulocyte maturity index (RMI) was calculated using subfractions of immature reticulocytes.

Patients with elevated levels of APO-1, lipocalin-2, and TNF-α had significantly lower RMI than those without elevations in these parameters. Compared with non-anemic individuals, anemic patients had significantly higher levels of APO-1, TNF-α, and lipocalin-2. Lipocalin-2 was negatively correlated with RMI and hemoglobin levels and positively correlated with APO-1, TNF-α, and IL-6 levels but not with erythropoietin and TRAIL levels. Patients in the highest quartile of lipocalin-2 levels exhibited significantly higher APO-1 levels than those in the lowest quartile of lipocalin-2 levels. Elevation of lipocalin-2 resulted in a 1.3-fold increase in the prevalence of low RMI (odds ratio: 1.314, 95% confidence interval, 1.011-2.612, p<0.001).

APO-1 and lipocalin-2 are associated with the development of anemia in inflammatory conditions, possibly by inhibiting reticulocyte production, particularly in conjunction with inflammatory cytokines.