Cytokines as potential biomarkers of liver toxicity induced by Dioscorea bulbifera L.

The present study is designed to search for the serum cytokine biomarker for liver injury induced by Dioscorea bulbifera L., which is a traditionally used herbal medicine in China. Mice were orally given various doses of ethyl acetate extract (EF) isolated from D. bulbifera for 12 days. The activity of serum alanine/aspartate transaminases (ALT/AST) was increased in EF (400 mg/kg)-treated mice. Histological assessment further confirmed EF (400 mg/kg)-induced liver injury. Results of a cytokine-antibody array demonstrated that there were 10 cytokines up-regulated and 1 cytokine down-regulated in EF (400 mg/kg)-treated mice. Enzyme-linked immunosorbent assay (ELISA) further confirmed the increased level of CD30 ligand (CD30L) and decreased level of interlukin-3 (IL-3) in EF-treated mice. In conclusion, our results demonstrate that the altered expression of CD30L and IL-3 may be potential biomarkers for hepatotoxicity induced by D. bulbifera.

[Prognostic significance of leukemia-associated phenotype in correlation with other biologic markers in acute myeloid leukemia patients]. / Identificarea semnificatiei prognostice a fenotipului asociat leucemiei in corelatie cu alti markeri biologici la pacientii cu leucemie acuta mieloblastica.

UNLABELLED: Leukemic cells have unique aberrant phenotypes, which permit identification of this cells at diagnose and in evolution of the disease. Signaling molecules with other cells and bone marrow stroma are part of the leukemic cells phenotype. Genetic and molecular abnormalities have the main prognostic significance and confer the leukemic cell status. The main aim of the current study is to identify correlation between recognized prognostic factors in acute myeloid leukemia (AML) patients and other phenotypic markers. MATERIAL AND METHOD: Imunophenotypic analysis (BDFACS CantoII, FACSDiva Software) was performed on peripheral blood/bone marrow aspirate samples of 56 patients diagnosed with AML (9 M0, 3 M1, 10 M2, 4 M3, 28 M4/M5, 1 M6, 1 M7) between 2007-2009 in Hematology Department of "Sf. Spiridon" Hospital Iasi. We used an extended panel of monoclonal antibodies and we determined the level of expression of cytokines receptors (IL3Ra, IL7R) and chemokines (CXCR4, CKR5). RESULTS: In our study, IL7R expression on AML blasts was significant correlate with low WBC count at diagnosis (p = 0.04) and with multilinear displasia (p = 0.01), high CXCR4 expression was correlate (p = 0.05) with lack of response at first induction therapy and CD123 (IL3Ra) expression was correlate with M4 FAB phenotype. Survival was negative influenced by presence of IL3R on AML blasts, but flt3 mutations, CXCR4, IL7R expression on leukemic cells, other phenotypic aberrancies did not influenced treatment response and survival in our patients population. CONCLUSION: Complete investigation of leukemic cells phenotype extended with cytokines/chemokines receptors at diagnostic is useful for correct characterization of the disease, for discover new prognostic categories and for better identification of minimal residual disease.

Role of prohepcidin, inflammatory markers and iron status in resistance to rhEPO therapy in hemodialysis patients.

The aim of our study was to assess possible relations between prohepcidin, iron status and inflammatory markers in hemodialysis (HD) patients, as well as its association with resistance to recombinant human erythropoietin (rhEPO) therapy. Fifty HD patients and 25 healthy controls were enrolled in the study. Among HD patients, 25 were non-responders and 25 were responders to rhEPO therapy. Complete blood cell count, reticulocyte count, and circulating levels of ferritin, iron, transferrin saturation, C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (s-IL2R), soluble transferrin receptor (s-TfR), IL-6 and prohepcidin were measured in all patients and controls. HD patients showed higher circulating levels of ferritin, s-TfR, CRP, IL-6, s-IL2R and prohepcidin, and lower levels of transferrin compared to healthy controls. Higher levels of s-TfR, CRP and lower levels prohepcidin were observed among non-responders compared to responders. Prohepcidin levels correlated negatively with s-TfR and reticulocyte count. The weekly rhEPO/kg dose was found to be positively correlated with CRP, hemoglobin and s-TfR. In conclusion, our data show that a close interaction exists between inflammation, iron status and prohepcidin serum levels that ultimately regulate intracellular iron availability. Prohepcidin and s-TfR, together with CRP, may prove to be good markers of resistance to rhEPO therapy in HD patients.

Plasmacytoid dendritic cell count on day 28 in HLA-matched related allogeneic peripheral blood stem cell transplant predicts the incidence of acute and chronic GVHD.

Dendritic cells (DC) are antigen-presenting cells involved in induction and regulation of immune responses. We investigated the impact of the number of infused and day 28 dendritic cells on the development of acute and chronic GVHD (aGVHD, cGVHD). Monocytoid (MC) and plasmacytoid (PC) dendritic cells were characterized as lin(-)HLA-DR(+)CD11c(+) and lin(-)HLA-DR(+)CD123(+), respectively. Sixty-eight consecutive patients who underwent HLA matched related granuloyte-colony stimulating factor (G-CSF) mobilized allogeneic PBSCT, from February 2005 to May 2006, were included in the analysis. Twenty-three patients developed aGVHD (grade II-IV) and 21 patients had cGVHD. On a univariate analysis the day 28 total DC and the day 28 MC and PC dendritic cells as continuous variables were significantly associated with development of aGVHD and cGVHD. Using an ROC plot analysis a cutoff value for total DC = 10.7/microL, MC = 9.7/microL, and PC = 4.5/microL on day 28 gave the highest likelihood ratios for aGVHD (2.7, 2.14, and 3.29, respectively). On a multivariate analysis, a low day 28 PC (

Compartmental imbalance and aberrant immune function of blood CD123+ (plasmacytoid) and CD11c+ (myeloid) dendritic cells in atopic dermatitis.

Atopic dermatitis (AD) is a pruritic, chronically relapsing skin disease in which Th2 cells play a crucial role in cutaneous and extracutaneous immune reactions. In humans, CD11c+CD123- myeloid dendritic cells (mDC) and CD11c-CD123+ plasmacytoid DC (pDC) orchestrate the decision-making process in innate and acquired immunity. Since the number and function of these blood dendritic cell (DC) subsets reportedly reflect the host immune status, we studied the involvement of the DC subsets in the pathogenesis of AD. Patients with AD had an increased DC number and a low mDC:pDC ratio with pDC outnumbering mDC in the peripheral blood compared with normal subjects and psoriasis patients (a Th1 disease model group). The mDC:pDC ratio was correlated with the total serum IgE level, the ratio of IFN-gamma-producing blood cells:IL-4-producing blood cells, and the disease severity. In vitro allogeneic stimulation of naive CD4+ cells with atopic DC showed that the ability of pDC for Th1 induction was superior or comparable to that of mDC. In skin lesions, pDC infiltration was in close association with blood vessels expressing peripheral neural addressins. Therefore, compartmental imbalance and aberrant immune function of the blood DC subsets may deviate the Th1/Th2 differentiation and thus induce protracted allergic responses in AD.

The relationship between interleukin-3-like activity and basophil production in chronic myeloid leukemia patients.

Increased basophil proliferation has been reported in patients with chronic myeloid leukemia (CML) both in vivo and in vitro. In this study we have examined the relationship between the release of interleukin-3-like activity (IL-3-LA) by mononuclear cells derived from CML patients and the development of basophils under culture conditions. The results indicate that cells from CML patients produce a high percentage of basophils under the applied experimental conditions. The IL-3-LA in the conditioned medium (CM) of these patients was much lower than that of the controls. Incubation of cells from CML patients with CM containing IL-3-LA resulted in its absorption, whereas cells from control subjects did not absorb the factor. This result may explain the discrepancy between the high basophil production and the low IL-3-LA observed in the CML patients and may indicate that leukemic cells possess receptors for IL-3-LA.

Immunoregulatory cell dysfunction in chronic B-cell leukemias.

Chronic B-cell malignancies are routinely characterized as B-cell clonal diseases that have signs and symptoms primarily related to the continuing expansion of these cells. This review discusses chronic lymphocytic leukemia, multiple myeloma and hairy cell leukemia from the perspective of secondary abnormalities in non-malignant cells. Thus, our main purpose is to elaborate on the alterations/abnormalities of the immunoregulatory (IR) cells in these diseases and focus on the qualitative and quantitative aspects of T-cells, natural killer (NK) cells and monocytes. The relevance of the IR-cell changes to the basic disease process and their complications are emphasized.