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Immunosuppressive Cytokines (immunosuppressive + cytokine)

Distribution by Scientific Domains
Medical Sciences85%

Selected Abstracts

Methylenedioxymethamphetamine (MDMA, ,Ecstasy'): a stressor on the immune system

IMMUNOLOGY, Issue 4 2004
Thomas J. Connor
Summary Drug abuse is a global problem of considerable concern to health. One such health concern stems from the fact that many drugs of abuse have immunosuppressive actions and consequently have the potential to increase susceptibility to infectious disease. This article is focused on the impact of the amphetamine derivative, methylenedioxymethamphetamine (MDMA; ,Ecstasy') on immunity. Research conducted over the last 5 years, in both laboratory animals and humans, has demonstrated that MDMA has immunosuppressive actions. Specifically, MDMA suppresses neutrophil phagocytosis, suppresses production of the pro-inflammatory cytokines tumour necrosis factor-, (TNF-,) and interleukin (IL)-1,, and increases production of the endogenous immunosuppressive cytokine (IL-10), thereby promoting an immunosuppressive cytokine phenotype. MDMA also suppresses circulating lymphocyte numbers, with CD4+ T cells being particularly affected, and alters T-cell function as indicated by reduced mitogen-stimulated T-cell proliferation, and a skewing of T-cell cytokine production in a T helper 2 (Th2) direction. For the most part, the aforementioned effects of MDMA are not the result of a direct action of the drug on immune cells, but rather caused by the release of endogenous immunomodulatory substances. Consequently, the physiological mechanisms that are thought to underlie the immunosuppressive effects of MDMA will be discussed. As many of the physiological changes elicited by MDMA closely resemble those induced by acute stress, it is suggested that exposure to MDMA could be regarded as a ,chemical stressor' on the immune system. Finally, the potential of MDMA-induced immunosuppression to translate into significant health risks for abusers of the drug will be discussed. [source]

Circulating interleukin-10 and interleukin-12 in Parkinson's disease

ACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009
M. Rentzos
Background,,, Interleukin (IL)-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines. IL-10 is a pleiotropic cytokine produced by both lymphocytes and mononuclear phagocytes including microglia. Recent studies demonstrated the neuroprotective effect of IL-10. There is little information about the involvement of IL-12 or IL-10 in the pathophysiology of Parkinson's disease (PD). Objectives,,, The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with PD and to investigate whether IL-10, an immunosuppressive cytokine, may have a neuroprotective effect in the pathogenesis of PD. Patients and methods,,, We measured using immunoassay serum IL-12 and IL-10 levels in 41 patients with PD in comparison with serum levels in 19 healthy subjects (controls) age and sex matched. IL-12 and IL-10 levels were tested for correlation with sex, age, disease duration, Hoehn and Yahr stage and the UPDRS III score. Results,,, The PD group presented with significantly increased IL-10 levels when compared with the control group (P = 0.02). The increase observed was not affected by the treatment status. A strong and significant correlation between IL-10 and IL-12 levels was observed in patients with PD (RS = 0.7, P < 0.000001). Conclusions,,, Our findings suggest that IL-10 may be involved in the pathogenetic mechanisms of PD. The elevation of IL-10 and the significant correlation between IL-10 and IL-12, a proinflammatory cytokine, may suggest that immunological disturbances and neuroprotective mechanisms are involved in patients with PD. [source]

Molecular determinants of UV-induced immunosuppression

EXPERIMENTAL DERMATOLOGY, Issue 2002
Agatha Schwarz
Abstract: It is almost three decades ago that it was discovered that ultraviolet radiation (UV) can compromise the immune system. UV suppresses immune responses in several ways. It inhibits the function of antigen-presenting cells, induces T cells with suppressor activity and induces the release of immunosuppressive cytokines. The latter phenomenon is mainly responsible for systemic immunosuppression. Although UV can also target cytoplasmic and cell membrane components, UV-induced DNA damage has been recognized as the most important molecular structure in mediating UV-induced immunosuppression. Recently, it was observed that interleukin-12 (IL-12), which antagonizes UV-induced immunosuppression, can accelerate the removal of UV-induced DNA lesions, probably via inducing DNA repair. Hence, it is tempting to speculate that the activity of IL-12 to reduce UV-induced immunosuppression may be due at least partially to this new biological activity of IL-12. [source]

Regulatory T cells and intestinal homeostasis

IMMUNOLOGICAL REVIEWS, Issue 1 2005
Janine L. Coombes
Summary:, Murine models of inflammatory bowel disease (IBD) are useful tools for the study of the pathogenesis and regulation of intestinal inflammation. Colitis can be induced in immune-deficient mice following transfer of populations of T cells or following infection with Helicobacter hepaticus and other intestinal pathogens. In these situations, colitis occurs as a result of the absence of a specialized population of regulatory cells, as transfer of CD4+CD25+ T cells prevents disease. Importantly, from a clinical perspective, CD4+CD25+ T cells can also reverse an established colitis. CD4+CD25+ T cells proliferate both in the secondary lymphoid organs and at the site of inflammation, suggesting that regulation occurs both locally and systemically. CD4+CD25+ T cells are not only capable of regulating other T cells but are also capable of suppressing components of the innate immune system. Control of colitis is dependent on the presence of the immunosuppressive cytokines interleukin-10 and transforming growth factor-,, although their roles are divergent and complex. Regulatory T cells represent one of the host's mechanisms to prevent immune pathology during chronic immune stimulation. Enhancement of regulatory T-cell activity may be useful to control autoreactive T-cell responses and inhibit harmful inflammatory diseases such as asthma and IBD. [source]

Immune manipulation of advanced breast cancer: An interpretative model of the relationship between immune system and tumor cell biology

MEDICINAL RESEARCH REVIEWS, Issue 3 2009
Andrea Nicolini
Abstract This review summarizes some recent clinical immunological approaches with cytokines and/or antibodies for therapy of advanced breast cancer. It considers the recent advances in genetics and molecular tumor biology related to impaired immunosurveillance involving cytokines and growth factors to explain clinical results. Evasion of the host immune attack might be induced by the following groups of mechanisms: (a) tumor dependent (genomic instability, HLA class I antigen abnormalities, upregulation of fetal type nonclassical HLA class I molecules, epitope immunodominance, apoptosis inhibition by defective death receptor signaling, apoptosis of activated T cells, tumor cannibalism and constitutive activation of signal transducer, and activator of transcription-3 (Stat 3) and nuclear factor-,B (NF-kB) signaling); (b) host dependent (CD4+CD25+ regulatory T cells (T reg), CD4+ T cells anergy, Th2 antitumor immunity diversion and myeloid suppressor cells); (c) tumor and host dependent (lack of co-stimulation molecules, immunosuppressive cytokines (vascular endothelial growth factor (VEGF), interleukin (IL)-10, prostaglandin (PG)E2, transforming growth factor (TGF)-,)). Cytokines and growth factors are involved in virtually all three types of mechanisms. These mechanisms are integrated with the current knowledge of tumor growth and inhibited apoptosis primarily mediated by cytokines and growth factors to propose an interpretation of the relationships among tumor cells, tumor stroma, and tumor-infiltrating lymphocytes. Tumor growth, defective immunorecognition and immunosuppression are the three principal effects considered responsible for immune evasion. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 3, 436-471, 2009 [source]

Dominant IL-10 and TGF-, mRNA Expression in ,,T Cells of Human Early Pregnancy Decidua Suggests Immunoregulatory Potential

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2002
OLGA NAGAEVA
PROBLEM:,To examine the cytokine gene expression in ,,T-cells from human early pregnancy decidua. METHOD OF STUDY:,The cytokine messenger RNA (mRNA) expression in isolated decidual T-cell receptor (TCR),,+/CD56+ and TCR,, single positive cells was investigated with a panel of cytokine primers and probes selected to distinguish between T helper (Th)1, Th2, Th3 and regulatory T-cells (Tr1) type of immune response using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS:,TCR,,+/CD56+ cells express almost exclusively the immunosuppressive cytokines interleukin-10 (IL-10) and transforming growth factor (TGF)-,. The TCR,, single positive cells enhance their transcription of IL-10 and TGF-,, compared with the TCR,,+/CD56+ cells and additionally express mRNA for IL-1, and IL-6. CONCLUSIONS:,The present findings suggest that ,,T cells in normal pregnancy create a cytokine milieu promoting immunotolerance to the fetus. We hypothesize that through the production of the immunosuppressive cytokines IL-10 and/or TGF-, the ,,T cells could function directly as regulatory T cells or induce the differentiation of Th0 TCR,,+ cells into regulatory/suppresser cells. [source]

Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase,positive dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity disease models

ARTHRITIS & RHEUMATISM, Issue 2 2009
Nicole R. Bianco
Objective We have demonstrated previously that dendritic cells (DCs) modified with immunosuppressive cytokines, and exosomes derived from DCs can suppress the onset of murine collagen-induced arthritis (CIA) and reduce the severity of established arthritis. Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme that is important for immune regulation and tolerance maintenance. DCs expressing functional IDO can inhibit T cells by depleting them of essential tryptophan and/or by producing toxic metabolites, as well as by generating Treg cells. This study was undertaken to examine the immunosuppressive effects of bone marrow (BM),derived DCs genetically modified to express IDO, and of exosomes derived from IDO-positive DCs. Methods BM-derived DCs were adenovirally transduced with IDO or CTLA-4Ig (an inducer of IDO), and the resulting DCs and exosomes were tested for their immunosuppressive ability in the CIA and delayed-type hypersensitivity (DTH) murine models. Results Both DCs and exosomes derived from DCs overexpressing IDO had an antiinflammatory effect in CIA and DTH murine models. The suppressive effects were partially dependent on B7 costimulatory molecules. In addition, gene transfer of CTLA-4Ig to DCs resulted in induction of IDO in the DCs and in exosomes able to reduce inflammation in an IDO-dependent manner. Conclusion These results demonstrate that both IDO-expressing DCs and DC-derived exosomes are immunosuppressive and antiinflammatory, and are able to reverse established arthritis. Therefore, exosomes from IDO-positive DCs may represent a novel therapy for rheumatoid arthritis. [source]