Additive inhibition of dendritic cell allostimulatory capacity by alcohol and hepatitis C is not restored by DC maturation and involves abnormal IL-10 and IL-2 induction

被引:52
作者
Dolganiuc, A [1 ]
Kodys, K [1 ]
Kopasz, A [1 ]
Marshall, C [1 ]
Mandrekar, P [1 ]
Szabo, G [1 ]
机构
[1] Univ Massachusetts, Med Ctr, Dept Med, Div Gastroenterol, Worcester, MA 01605 USA
关键词
tumor necrosis factor alpha; interleukin-12; monocyte; ethanol; apoptosis;
D O I
10.1097/01.ALC.0000071745.63433.32
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
Background: Excessive alcohol use results in impaired immunity, and it is associated with increased incidence and progression of chronic hepatitis C virus (HCV) infection. Here we investigated the effects of HCV infection and alcohol on myeloid dendritic cells (DC) that are critical in antiviral immunity. Methods: Immature and mature DCs were generated from monocytes of chronic HCV infected patients (HCV-DC) and controls (N-DC) with IL-4 plus granulocyte-macrophage colony stimulating factor (GMCSF) in the presence or absence of alcohol (25 mM). DC allostimulatory capacity was tested in mixed lymphocyte reaction (MLR) and cytokine production by ELISA. Results: Allostimulatory capacity of HCV-DCs was reduced compared to N-DiCs and it was further inhibited by alcohol treatment (p < 0.01). MLR was also decreased with alcohol-treated N-DCs. DC phenotypic markers and apoptosis were comparable between HCV-DCs and N-DiCs irrespective of alcohol treatment. However, HCV-DCs and alcohol-treated N-DiCs exhibited elevated IL-10 and reduced IL-12 production. Reduced MLR with HCV-DCs and its further inhibition by alcohol coexisted with decreasing IL-2 levels (p < 0.017). DC maturation partially improved but failed to fully restore the reduced allostimulatory function of either alcohol-treated or alcohol-naive HCV-DCs (p < 0.018). Conclusions: Alcohol and HCV independently and together inhibit DC allostimulatory capacity, increase IL-10, reduce IL-12 and IL-2 production that cannot be normalized by DC maturation. HCV and alcohol interact to modulate innate and adaptive immune responses via dendritic cells.
引用
收藏
页码:1023 / 1031
页数:9
相关论文
共 64 条
[1]   Influence of chronic alcohol abuse on hepatitis C virus replication [J].
Anand, BS ;
Velez, M .
DIGESTIVE DISEASES, 2000, 18 (03) :168-171
[2]   Assessment of liver histology in chronic alcoholics with and without hepatitis C virus infection [J].
Anderson, S ;
Nevins, CL ;
Green, LK ;
El-Zimaity, H ;
Anand, BS .
DIGESTIVE DISEASES AND SCIENCES, 2001, 46 (07) :1393-1398
[3]   Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection [J].
Auffermann-Gratzinger, S ;
Keeffe, EB ;
Levy, S .
BLOOD, 2001, 97 (10) :3171-3176
[4]   Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection [J].
Bain, C ;
Fatmi, A ;
Zoulim, F ;
Zarski, JP ;
Trépo, C ;
Inchauspé, G .
GASTROENTEROLOGY, 2001, 120 (02) :512-524
[5]   Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[6]   Cross-priming versus cross-tolerance:: are two signals enough? [J].
Blankenstein, T ;
Schüler, T .
TRENDS IN IMMUNOLOGY, 2002, 23 (04) :171-173
[7]   Quantitative analysis of hepatitis C virus in peripheral blood and liver: Replication detected only in liver [J].
Boisvert, J ;
He, XS ;
Cheung, R ;
Keeffe, EB ;
Wright, T ;
Greenberg, HB .
JOURNAL OF INFECTIOUS DISEASES, 2001, 184 (07) :827-835
[8]   Pathogenesis, diagnosis and management of hepatitis C [J].
Boyer, N ;
Marcellin, P .
JOURNAL OF HEPATOLOGY, 2000, 32 :98-112
[9]  
Brossart P, 2000, CANCER RES, V60, P4485
[10]   RNA based Vaccines [J].
Cannon, G ;
Weissman, D .
DNA AND CELL BIOLOGY, 2002, 21 (12) :953-961