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Cytokine Environment (cytokine + environment)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Intra-tumoral Salmonella typhimurium induces a systemic anti-tumor immune response that is directed by low-dose radiation to treat distal disease

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008
Francesca Avogadri
Abstract Salmonella typhimurium is a facultative anaerobic bacterium able to multiply preferentially in tumors and inhibit their growth. The mechanisms through which Salmonella exerts its anti-cancer properties are not fully understood. We recently showed that intra-tumoral Salmonella injection results not only in the regression of even bulky tumor masses, but also impacts on the growth of distant untreated lesions. Here we describe how Salmonella exerts its systemic anti-cancer effects and means to potentiate them. The outburst of an early inflammatory reaction in the treated tumor promotes the development of an immunostimulatory cytokine environment both locally and in the draining lymph node. Within the next 10,days, an efficient cross-presentation of endogenous tumor antigens by dendritic cells at the tumor-draining lymph node leads to the priming of effective anti-tumor CD8+ T cell responses. This potentially broadly reactive T cell repertoire can be directed to other pre-established melanomas by low-dose radiotherapy enhancing the Salmonella anti-cancer effect. We demonstrate that Salmonella -based therapy coupled to low-dose radiotherapy dampens tumor immune escape mechanisms at different levels and allows controlling systemic disease in a CD8+ T cell-dependent manner. [source]

CCR6 has a non-redundant role in the development of inflammatory bowel disease

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2003
Rosa Varona
Abstract Antigen-loaded tissues such as the intestinal mucosa must simultaneously elicit appropriate immune response to innocuous bacteria and food proteins, and to potentially harmful antigens. Impairment of the mechanisms controlling this response may mediate the excessive immune reaction that can lead to tissue destruction and inflammatory intestinal diseases, including inflammatory bowel disease. The intestinal epithelium influences local immune responses through the expression of adhesion molecules, costimulatory factors, cytokines and chemokines. CCL20, a ,-chemokine expressed in epithelia from colon and other intestinal tissue, plays a role in immune responses of intestinal mucosa, as deduced from the defects in intestinal leukocyte homeostasis shown by mice lacking CCR6, the CCL20 receptor. We studied the response of CCR6-deficient mice in two models of inflammatory bowel disease. The data show that absence of CCR6 resulted in less severe intestinal pathology in animals treated with dextran sodium sulfate. Conversely, CCR6 deficiency alters leukocyte homeostasis and the cytokine environment in the intestinal mucosa; these changes are sufficient to confer susceptibility to trinitrobenzene sulfonic acid-induced intestinal inflammation in the otherwise resistant C57BL/6J mouse strain. These results suggest that the CCR6/CCL20 axis has a critical, non-redundant role in the in vivo control of immune responses in the intestine. [source]

Hepatocytes as cytotoxic effector cells can induce cell death by CD95 ligand-mediated pathway,

HEPATOLOGY, Issue 6 2006
Clifford S. Guy
The liver plays an increasingly recognized role in the host's immune responses. The direct contribution of hepatocytes as effector cells to local immunity, pathogen containment, and liver disease is not determined. This in vitro study examined whether hepatocytes can eliminate other cells via a CD95 ligand (CD95L or FasL)/CD95 (Fas),mediated mechanism and whether this cytotoxic activity can be modulated by cytokines such as interferon gamma (IFN-,) or tumor necrosis factor alpha (TNF-,). We have found that normal woodchuck and human hepatocytes, both cultured and primary freshly isolated, as well as human HepG2 cells, intrinsically transcribe not only CD95 but also CD95L when examined by reverse transcription-polymerase chain reaction (RT-PCR) assays. The functional competence of CD95L, which was detectable in hepatocytes and HepG2 cells by Western blotting, was confirmed in bioassays by induction of apoptosis of CD95-bearing P815 and LS102.9 cell targets and validated by inhibition of the cell killing with CD95 antagonistic antibody or with a general caspase inhibitor. Furthermore, exposure of cultured hepatocytes to IFN-, or their stable transfection with IFN-, cDNA or TNF-, cDNA increased hepatocyte CD95L/CD95,mediated cell killing. In conclusion, hepatocytes express both CD95L and CD95 and they can induce death of other cells by a CD95L-dependent mechanism. IFN-, and, to a lesser extent, TNF-, can enhance hepatocyte CD95L-mediated cytotoxicity. This suggests that the local cytokine environment may modulate the hepatocyte contribution to liver immunity. (HEPATOLOGY 2006;43:1231,1240.) [source]

A T2 cytokine environment may not limit T1 responses in human immunodeficiency virus patients with a favourable response to antiretroviral therapy

IMMUNOLOGY, Issue 1 2006
Patricia Price
Summary Low-level production of interferon-, (IFN-,) marks human immunodeficiency virus (HIV)-induced immunodeficiency and has been ascribed to a bias towards T2 cytokines. This was investigated in two cross-sectional studies of HIV patients who were immunodeficient when they began antiretroviral therapy (ART) and had stable increases in CD4 T-cell counts. Blood leucocytes were assessed unstimulated or after stimulation with cytomegalovirus (CMV), anti-CD3 or mitogen. IFN-, and interleukin (IL)-5 responses were initially assessed by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). We then adopted a sensitive reverse transcription,polymerase chain reaction (RT,PCR) system to assess IFN-,, IL-5, IL-4 and IL-4,2 (an inhibitory splice variant of IL-4) mRNA. The results were correlated with putative serological markers of a T1 [lymphocyte activation gene-3 (LAG-3), CD26] or a T2 [CD30, immunoglobulin E (IgE)] cytokine environment. IL-5 production and IgE levels were elevated in patients. IgE levels did not correlate with IFN-,, but showed an inverse correlation with IL-5 released in culture (P = 0·05). The levels of IL-4, IFN-,, IL-5 and IL-4,2 mRNA were correlated after anti-CD3 stimulation, where IL-5 was the best predictor of IFN-, mRNA (P = 0·006). Weak positive correlations were evident between CD30 and cytokine mRNA levels, whilst IgE correlated inversely with IL-4, IL-4,2, IL-5 and IFN-, mRNA levels. These analyses provide no evidence for an inverse relationship between T1 and T2 cytokine responses in HIV patients, but suggest that the elevation of IgE marks low cytokine responses. [source]

Tumor necrosis factor- , and transforming growth factor- , reflect severity of liver damage in primary biliary cirrhosis

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2002
MANUELA NEUMAN
Abstract Background and Aims The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor-, (TNF-,) and transforming growth factor-, (,GF-,), and the effect of ursodeoxycholic acid (UDCA) in modifying the cytokine environment in patients with PBC has remained largely unstudied. Our aims were to determine: (i) the relationship between serum levels of TNF-, and TGF-, and the severity of PBC; and (ii) the effects of UDCA therapy on TNF-, and TGF-, levels in patients with PBC. Methods We studied 90 patients who had been treated with UDCA (53 patients) or placebo (37 patients) for 2 years as part of a randomized, double-blind, controlled trial. Patients were divided into histological stage I/II or stage III/IV disease. Serum TNF-, and TGF-, levels were quantified by enzyme-linked immunoabsorbent assay. Results Baseline levels of TNF-, were significantly greater in patients with stage III/IV compared to stage I/II disease. After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF-, levels and progression risk score compared to placebo-treated patients. TNF-, and TGF-, levels were significantly reduced compared to baseline levels in the UDCA-treated group after 2 years, while there was no significant change in the levels of placebo-treated patients. Conclusions Serum TNF-, and TGF-, levels may reflect severity of disease in patients with PBC. The beneficial effects of UDCA therapy may be explained by lowering serum levels of these two cytokines. [source]

In vitro antigen presenting cell-derived IL-10 and IL-6 correlate with Trichuris muris isolate-specific survival

PARASITE IMMUNOLOGY, Issue 3 2009
R. D'ELIA
SUMMARY Trichuris muris, the mouse whipworm, is used as a laboratory model of the human parasite T. trichiura. Three laboratory isolates of T. muris exist , the E, J and S isolates. Previous data have shown that the S isolate survives to chronicity in C57BL/6 mice unlike the E and J isolates, which are expelled. The ability of the S isolate to persist is thought to be due to it secreting unique excretory/secretory antigens, which interact with APCs such that protective T cell responses do not develop. To determine whether APCs respond differently to E/S antigens from the three isolates we cultured isolate-specific E/S with bone marrow-derived macrophages (BMM,) and dendritic cells (BMDCs) in vitro. Markers of co-stimulation and levels of MHC-II were analysed by FACS and cytokine levels in supernatants quantified. E/S antigens from the S isolate consistently stimulated significantly higher levels of IL-10 and IL-6 from both macrophages (F4/80+CD11b+CD11c,) and dendritic cells (CD11c+CD11b+F4/80,) compared to J and E isolate E/S. If these in vitro differences in APC-derived cytokines, particularly IL-10, are biologically significant in vivo, they may contribute to the S isolate survival, by creating a regulatory cytokine environment in which protective immune responses are less effective. [source]

Comparison of Vaginal Cytokine Collection Methods

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2006
Constance J. Faro
Objective The objective of our study was to correlate the interleukin-6 (IL-6) concentrations detected in patient-collected specimens with provider-collected specimens and compare the reproducibility of the methods. Study design All enrolled participants underwent pelvic examination with collection of cytokine samples by the provider and also collected samples themselves using vaginal swabs. The order of sample collection was randomly assigned. All samples were frozen at ,80°C for batch analysis. A commercial enzyme-linked immunosorbent assay was used to determine the concentrations of IL-6 in all samples. Results IL-6 concentrations from wicks and swabs were correlated in a linear fashion (r = 0.67, P < 0.001). IL-6 concentrations in the two swabs (r = 0.94, P < 0.001) and the two wicks (r = 0.71, P < 0.001) were correlated in a linear fashion, although there was more variability in wick specimens. Conclusion IL-6 concentrations can be reproducibly measured using either method. The ease of patient swab collection and the correlation with provider-collected specimens may make frequent assessment of the vaginal cytokine environment more acceptable to patients. [source]

Th17 and natural Treg cell population dynamics in systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 5 2009
Ji Yang
Objective To investigate the relative abundance and activities of Th17 cells and natural Treg cells in systemic lupus erythematosus (SLE). Methods Blood samples were collected from 50 adult patients with SLE. Samples were processed to detect Th17 cells and natural Treg cells by flow cytometry, and related gene expression was assessed by real-time reverse transcription,polymerase chain reaction. Skin biopsy specimens were collected for histologic assessment. The function of Th17 cells in relation to human umbilical vein endothelial cells (HUVECs) was studied in vitro. Th17 cells were also examined in lupus-prone MRL/Mp- lpr/lpr (MRL/lpr) mice. Results We demonstrated the presence of Th17 cells among the peripheral blood mononuclear cells (PBMCs) and in the involved organs of patients with active SLE. Both the percentage of circulating Th17 cells and the ability to produce interleukin-17A (IL-17A) were increased in samples derived from patients with active SLE. The number of Th17 cells increased during SLE flare, especially in patients with vasculitis, and decreased following certain treatments. We observed that IL-17A from patients with SLE could induce adhesion molecule messenger RNA expression in HUVECs and adhesion of T cells to HUVECs. An increase in the percentage of Th17 cells was correlated with natural Treg cell depletion during disease flare. Finally, expansion of the Th17 cell population was detected in MRL/lpr mice. Conclusion SLE flare might be linked to the expansion of the Th17 cell population and the depletion of natural Treg cell subpopulations. Expansion of the Th17 cell population might be related to a distinct cytokine environment in active SLE. Th17 cells and microenvironmental IL-17A are involved in vascular inflammation in SLE. Antagonism of Th17 cells by IL-17A,blocking antibodies should be explored as a treatment of SLE. [source]