Immune regulation of hydrogen sulfide in children with acute lymphoblastic leukemia.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
Gaseous molecule H2S might participate in the process of immune regulation in pediatric ALL through modulating transcription and expression of cytokines.
Department of Pediatrics, Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Shuxu
S
Du
Health Science Center, Peking University, Beijing 100191, China.
Yongrui
Y
Jia
Department of Pediatrics, Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Hong
H
Tang
Department of Pediatrics, Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Yangling
Y
Sun
Department of Pediatrics, Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Wanshui
W
Wu
Department of Pediatrics, Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Liming
L
Sun
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Junbao
J
Du
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China.
Bin
B
Geng
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China.
Chaoshu
C
Tang
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. Email: jinhongfang51@126.com.
Hongfang
H
Jin
D002648:Child; D002675:Child, Preschool; D003542:Cystathionine gamma-Lyase / Q000097:blood; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
C508609:IL10 protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide