interleukin-8 and Polycythemia-Vera

Chronic myeloproliferative neoplasms are characterized by clonal hematopoiesis and persistent inflammatory reaction. In this study, the clinical significance and prognostic impact of several inflammatory markers were evaluated in patients with BCR/ABL-negative myeloproliferative malignancies.. Serum levels of interleukin-8 (IL-8) and lymphoid-associated activation markers - soluble interleukin-2 receptor (sIL-2R) and immunoglobulin-free light chains (FLC) - were evaluated in patients with primary myelofibrosis (MF), post-polycythemia vera MF, and post-essential thrombocythemia MF, and compared with the levels in healthy donors.. In 57 MF patients, sIL-2R excess correlated with transfusion-dependent anemia (p = 0.03) and splenomegaly (p = 0.02). There were no statistically significant correlations between sIL-2R and IL-8 levels, but the plasma concentration of κ-FLC positively correlated with the IL-8 level (p = 0.027). In univariate analysis, increased levels of IL-8 (p = 0.016) and sIL-2R (p = 0.010) significantly reduced 1-year overall survival. Only elevated sIL-2R rate retained significance (p = 0.02) in multivariate analysis when Dynamic International Prognostic Scoring System plus (DIPSSplus) risk stratification was added.. We observed an association between FLC and proinflammatory cytokine hyperexpression. Serum cytokine levels and FLC might be a promising approach to predicting and monitoring treatment response in MF patients.

Topics: Aged; Anemia; Female; Humans; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Inflammation Mediators; Interleukin-8; Male; Middle Aged; Polycythemia Vera; Primary Myelofibrosis; Prognosis; Receptors, Interleukin-2; Reference Values; Statistics as Topic; Survival Analysis; Thrombocythemia, Essential

Endogenous erythroid colonies (EECs), formed in vitro without erythropoietin (EPo) or other exogenous cytokines, are characteristic of Polycythemia vera (PV). Our aim was to identify specific conditions of culture of bone marrow (BM) progenitors allowing formation of erythroid colonies without EPo.. BM mononuclear cells (BMMCs), purified CD34+ cells, and purified CD36+ erythroid progenitors were cultured in serum-free media without and with cytokines: EPo, stem cell factor (SCF), and interleukin (IL)-11 and IL-8, produced by BM stromal cells and found elevated in PV.. EECs were formed in PV cultures of either BMMCs or CD34+ cells, which include cytokine-secreting cells, but not in cultures of purified CD36+ erythroid progenitors (EP). Despite expression of V617F JAK-2, no constitutive activation of JAK-2, Stat-5, or Erk-1/2 was detected in erythroblasts issued from PV CD36+ progenitors. However, when SCF was provided, PV CD36+ progenitors formed erythroid colonies without EPo. The ability to form erythroid colonies with SCF alone was conferred to BM progenitors of healthy donors and secondary erythrocytosis by exposure to IL-11 and IL-8. Both IL-11 and IL-8 enhanced formation of erythroid colonies in response to EPo and interfered with the activation of Erk-1/2 and Stat-5 induced, respectively, by SCF and EPo in erythroblasts. Anti-IL-11 antibody inhibited formation of erythroid colonies by PV BMMCs and CD34+ cells.. The data indicate that PV erythroid progenitors remain cytokine-dependent and that normal BM progenitors exposed to IL-11 and IL-8 can acquire the ability to form erythroid colonies without EPo.

Topics: Bone Marrow Cells; Cell Culture Techniques; Coculture Techniques; Cytokines; Erythroid Precursor Cells; Erythropoietin; Hematopoietic Stem Cells; Humans; Interleukin-11; Interleukin-8; Polycythemia Vera; Signal Transduction

We studied the production of interleukin (IL)-11 and IL-8, two cytokines known to affect erythropoiesis, in polycythemia vera (PV). In vivo, IL-11 was detected more frequently in serum and bone marrow (BM) plasma of PV patients than in controls (healthy donors and patients with idiopathic erythrocytosis (IE)). In addition, serum IL-11 levels of PV patients were higher than those of controls. IL-8 was elevated in serum of both PV and IE patients (respective median levels: 38.6 and 242pg/ml, vs 4.4pg/ml for healthy donors). BM plasma IL-8 levels of PV patients (508pg/ml) were significantly higher than those of IE patients (120pg/ml). In vitro, bone marrow (BM) stromal cells (BMSC) of PV patients produced significantly more IL-11 (x6.4) and IL-8 (x8.3) than BMSC of healthy donors or IE patients. In conclusion, both IL-11 and IL-8 are overproduced in PV, apparently by BMSC; IL-8 is also overproduced in IE, by cells other than BMSC.

Topics: Bone Marrow Cells; Cells, Cultured; Humans; Interleukin-1; Interleukin-11; Interleukin-8; Polycythemia; Polycythemia Vera; Stromal Cells