Changes of sulfur dioxide, nuclear factor-κB, and interleukin-8 levels in pediatric acute lymphoblastic leukemia with bacterial inflammation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bacterial inflammation is a common complication in patients with leukemia, and sulfur dioxide (SO2) is a bioactive molecule in modulating Gram-negative bacilli infection. This study aimed to examine the changes in SO2, nuclear factor-κB (NF-κB), and interleukin-8 (IL-8) levels in pediatric acute lymphoblastic leukemia (ALL) with Gram-negative bacterial inflammation.</p><p><b>METHODS</b>Fifty-five ALL children were enrolled in this study, including 30 males and 25 females, aged 3-13 years, and the median age was 7.8 years. All these children who accepted chemotherapy for ALL were divided into the control group (before chemotherapy), the infection group (after chemotherapy with infection), and the recovery group (the infection was controlled after 1 week). The serum level of SO2 was detected using high performance liquid chromatography with fluorescence assay, and NF-κB and IL-8 levels were measured by enzyme-linked immunosorbent assay (ELISA). Human THP-1 cells were cultured, induced, and differentiated into macrophages, which were divided into five groups and each group was cultured with different stimulators: lipopolysaccharide (LPS) group, LPS+L-aspartate-β-hydroxamate (HDX) group, LPS+SO2 group, SO2, and control groups. NF-κB level and IL-8 protein contents by ELISA were examined in each group.</p><p><b>RESULTS</b>In comparison with those of the control group, levels of serum SO2, NF-κB, and IL-8 of the infection group were significantly increased (P < 0.05), while those of the recovery group were significantly decreased (P < 0.05). A positive correlation was found between levels of serum SO2 and intracellular NF-κB/IL-8, and the correlation coefficients were 0.671 and 0.798 (P < 0.05), respectively. According to the results found in human THP-1 cells, levels of NF-κB and IL-8 in LPS group were significantly increased compared with those of the control group (P < 0.05); when compared with those in LPS group, levels of NF-κB in LPS+HDX group further increased significantly (P < 0.05); however, the NF-κB levels of LPS+SO2 group decreased significantly (P < 0.05).</p><p><b>CONCLUSION</b>SO2 may play an anti-inflammatory role during the process of inflammation by inhibiting the activation and transcription of NF-κB.</p>

Immune regulation of hydrogen sulfide in children with acute lymphoblastic leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute lymphoblastic leukemia (ALL) and chemotherapy can cause immune imbalance, and gaseous molecule hydrogen sulfide (H2S) can participate in the process of immune response. This study aimed to investigate the immune regulation of H2S in pediatric ALL.</p><p><b>METHODS</b>Children (n = 78) with ALL admitted during 2010-2013 were included in this study. Two blood samples were collected in period of before chemotherapy, bone marrow remission and two days after chemotherapy, respectively. Serum contents of H2S and cytokines, including interleukin-1β (IL-1β), interleukin-2 (IL-2), interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10) and macrophage inflammatory protein-1α (MIP-1α), were detected using ELISA method. Stepwise regression was used to analyze the correlation between H2S and cytokines. Furthermore, human Jurkat cells were cultured in vitro, and nucleoprotein of Jurkat cells and peripheral blood mononuclear cells (PBMCs) were collected, contents of cystathionine γ-lyase (CSE) and certain cytokines were measured by Western blotting.</p><p><b>RESULTS</b>Serum concentrations of H2S, IL-1β, IL-6, IL-10 and MIP-1a in children with ALL were increased significantly (P < 0.01), while concentrations of IL-2, TNF-α, IFN-γ and IL-4 decreased obviously (P < 0.01). In patients after chemotherapy, concentrations of H2S and IL-10 were decreased significantly (P < 0.05), but IL-4 and IFN-γ concentrations increased markedly (P < 0.05). At remission stage, H2S, IL-1β, IL-4, IL-6, IL-10 and MIP-1α concentrations were further decreased markedly (P < 0.05), but concentrations of IL-2, TNF-α and IFN-γ increased again (P < 0.05). Protein contents of CSE, IL-10, IL-4 and IL-2 of PBMCs also increased markedly in children with ALL. Moreover, changes of CSE protein contents of PBMCs were consistent with serum H2S contents, and there were significant correlation between H2S and certain cytokines based on stepwise regression analysis. Furthermore, compared with those of PBMCs group, in vitro study indicated that Jurkat cells of H2S group expressed IFN-γ, IL-10, IL-4 and IL-2 protein increased obviously (P < 0.05), while IL-4, IL-2 and CSE expression of PPG group decreased markedly (P < 0.05).</p><p><b>CONCLUSION</b>Gaseous molecule H2S might participate in the process of immune regulation in pediatric ALL through modulating transcription and expression of cytokines.</p>