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1.
Am J Hematol ; 71(3): 177-83, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12410572

ABSTRACT

B-chronic lymphocytic leukemia (B-CLL) patients have a high prevalence of autoimmune phenomena, mainly autoimmune hemolytic anemia (AIHA). Immunoregulatory cytokines play a role in the regulation of both autoimmunity and leukemic B-cell growth. Mitogen-stimulated direct antiglobulin test (MS-DAT) is a recently described test able to disclose latent anti-RBC autoimmunity in AIHA. We investigated the prevalence of anti-RBC autoimmunity by MS-DAT and the pattern of cytokine production by PHA-stimulated whole blood cultures from 69 B-CLL patients and 53 controls. Results showed that anti-RBC IgG values in unstimulated, PHA-, PMA-, and PWM-stimulated cultures were significantly higher in B-CLL patients compared with controls. In B-CLL, the prevalence of anti-RBC autoimmunity was 28.9% by MS-DAT, compared with 4.3% by the standard DAT. Production of IFN-gamma, IL-2, IL-13, TNF-alpha, sCD23, and sCD30 was significantly increased in all B-CLL patients compared with controls, whereas there was no difference in IL-4, IL-6, IL-10, and TGF-beta production. Multivariate analysis showed that IL-4 was significantly increased in MS-DAT-positive compared with -negative patients. Patients with autoantibody positivity displayed greater IFN-gamma production than negative patients. These data are in line with the hypothesis that autoimmune phenomena in B-CLL are associated with an imbalance towards a Th-2-like profile. The elevated prevalence of anti-RBC autoimmunity found by MS-DAT suggests that an underestimated latent autoimmunity exists in B-CLL.


Subject(s)
Antibodies, Anti-Idiotypic/immunology , Erythrocytes/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Anti-Idiotypic/analysis , Antibody Formation , Autoimmunity , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Phytohemagglutinins , Pokeweed Mitogens/pharmacology , Reference Values , Tetradecanoylphorbol Acetate/pharmacology
2.
Clin Exp Immunol ; 123(3): 435-42, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11298131

ABSTRACT

Synergism between Mycobacterium tuberculosis (M. tuberculosis) and HIV-1 infections was demonstrated in several in vitro models and clinical studies. Here, we investigated their reciprocal effects on growth in chronically HIV-1-infected promonocytic U1 cells and in acutely infected monocyte-derived macrophages (MDM). Phagocytosis of M. tuberculosis induced HIV-1 expression in U1 cells, together with increased TNF-alpha production. M. tuberculosis growth, evaluated by competitive PCR, was greater in HIV-1-infected MDM compared to uninfected cells. M. tuberculosis phagocytosis induced greater TNF-alpha and IL-10 production in HIV-1-infected MDM than in uninfected cells. In uninfected MDM, addition of TNF-alpha and IFN-gamma decreased, whereas IL-10 increased M. tuberculosis growth. On the contrary, in HIV-1-infected MDM, addition of TNF-alpha and IFN-gamma increased, whereas IL-10 has no effect on M. tuberculosis growth. TNF-alpha seems to play a pivotal role in the enhanced M. tuberculosis growth observed in HIV-1-infected MDM, being unable to exert its physiological antimycobacterial activity. Here, for the first time we demonstrated an enhanced M. tuberculosis growth in HIV-1-infected MDM, in line with the observed clinical synergism between the two infections.


Subject(s)
HIV-1/growth & development , Macrophages/microbiology , Macrophages/virology , Mycobacterium tuberculosis/growth & development , Tumor Necrosis Factor-alpha/biosynthesis , Chemokines/biosynthesis , HIV Infections/microbiology , Humans , Interferon-gamma/biosynthesis , Interferon-gamma/pharmacology , Interleukin-10/biosynthesis , Interleukin-10/pharmacology , Phagocytosis , Tumor Necrosis Factor-alpha/pharmacology , U937 Cells
3.
Clin Exp Immunol ; 119(1): 123-9, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10606973

ABSTRACT

We investigated the in vitro effect of the water-soluble, highly stable thalidomide analogue CC-3052 on HIV-1 expression and TNF-alpha production in latently infected promonocytic U1 cells, acutely infected T cells and monocyte-derived human macrophages (MDM), and in mitogen-stimulated ex vivo cultures from patients with primary acute HIV-1 infection. HIV-1 expression was assessed by Northern blot analysis of RNAs, and ELISA for p24 antigen release and reverse transcriptase (RT) activity. TNF-alpha expression was evaluated by RT-polymerase chain reaction (PCR)-ELISA for mRNA and ELISA for protein secretion. We demonstrated that CC-3052 is able to inhibit HIV-1 expression, as evaluated by mRNA, p24 release and RT activity, in phorbol myristate acetate (PMA)- and cytokine-stimulated U1 cells. Furthermore, CC-3052 inhibited HIV-1 expression, as evaluated by p24 and RT activity, in acutely infected MDM and T cells. As far as TNF-alpha is concerned, CC-3052 significantly reduced TNF-alpha mRNA and protein secretion in PMA-stimulated U937 and U1 cells, and in PMA-stimulated uninfected and acutely infected MDM. Consistently, the addition of CC-3052 reduced TNF-alpha production in phytohaemagglutinin (PHA) and lipopolysaccharide (LPS)-stimulated whole blood cultures from patients during the primary acute phase of HIV-1 infection. Since TNF-alpha is among the most potent enhancers of HIV-1 expression, the effect of CC-3052 on TNF-alpha may account for its inhibitory activity on HIV-1 expression. Given the well documented immunopathological role of TNF-alpha and its correlation with viral load, advanced disease and poor prognosis, CC-3052 could be an interesting drug for the design of therapeutic strategies in association with anti-retroviral agents.


Subject(s)
HIV Infections/drug therapy , HIV Infections/immunology , HIV-1/drug effects , HIV-1/genetics , Thalidomide/analogs & derivatives , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Anti-HIV Agents/pharmacology , Base Sequence , Cell Line , DNA Primers/genetics , Gene Expression/drug effects , HIV Infections/virology , Humans , In Vitro Techniques , Macrophages/drug effects , Macrophages/immunology , Macrophages/virology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/virology , Tetradecanoylphorbol Acetate/pharmacology , Thalidomide/pharmacology , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/genetics , U937 Cells
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