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Increased IFN (increased + ifn)
Selected AbstractsAnti-inflammatory role of interleukin-15 in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2005Manuel A Silva MD Abstract Background: Interleukin (IL)-15 is overexpressed in intestinal tissue with active Crohn's disease (CD). However, its role in the pathogenesis of the disease remains uncertain. We studied the effects of IL-15 on colonic mucosal proinflammatory cytokine response in vitro using organ culture of human colonic explants. Methods: Colonic tissue was obtained from (1) resections in pediatric CD patients (inflamed and noninflamed) and (2) rectal biopsies in patients with CD undergoing colonoscopy (n = 31) and controls (n = 9). In preliminary experiments, explants from the resections were cultured in the presence or absence of a simulated TH1 stimulation using ionomycin (Io) and phorbol-myristate-acetate (PMA), with or without IL-15, or in medium alone. Rectal biopsies were cultured in the same conditions as above, with or without adding a monoclonal anti-IL-15 neutralizing antibody (mAb). Levels of interferon (IFN)-,, tumor necrosis factor (TNF)-,, and IL-2R, were measured by enzyme-linked immunosorbent assay. Results: IL-15, in the absence of Io + PMA, did not induce the expression of IFN-,, TNF-,, or IL-2R,. Only inflamed explants from resections stimulated with Io + PMA expressed IFN-,, TNF-,, and IL-2R,. This TH1 stimulatory effect was inhibited by IL-15 in a dose-dependent fashion. In rectal biopsy explants, inflamed, noninflamed CD, and control tissue responded to stimulation with Io + PMA (P < 0.05) with increased IFN-, and TNF-, (P < 0.05). This response was again inhibited by IL-15. The inhibitory effect of IL-15 was specifically reversed by anti-IL-15 mAb (P < 0.05). The data for the CD group were also analyzed according to the severity of colonic inflammation and medication use. Conclusions: Our results suggest a possible anti-inflammatory role for IL-15 in CD. We postulate that its overexpression in CD potentially represents a protective mechanism against the exaggerated TH1 immune response. [source] Interferon regulatory factor-1 acts as a powerful adjuvant in tat DNA based vaccination,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010Arianna Castaldello Genetic vaccines are safe cost-effective approaches to immunization but DNA immunization is an inefficient process. There is, therefore, a pressing need for adjuvants capable of enhancing the immunogenicity and effectiveness of these vaccines. This is particularly important for diseases for which successful vaccines are still lacking, such as cancer and infectious diseases including HIV-1/AIDS. Here we report an approach to enhance the immunogenicity of DNA vaccines involving the use of transcription factors of the Interferon regulatory factor (IRF) family, specifically IRF-1, IRF-3, and IRF-7 using the tat gene as model antigen. Balb/c mice were immunized by three intramuscular inoculations, using a DNA prime-protein boost protocol, with a DNA encoding tat of HIV-1 and the indicated IRFs and immune responses were compared to those induced by vaccination with tat DNA alone. In vivo administration of plasmid DNA encoding IRF-1, or a mutated version of IRF-1 deleted of the DNA-binding domain, enhanced Tat-specific immune responses and shifted them towards a predominant T helper 1-type immune response with increased IFN-, production and cytotoxic T lymphocytes responses. Conversely, the use of IRF-3 or IRF-7 did not affect the tat -induced responses. These findings define IRF-1 and its mutated form as efficacious T helper 1-inducing adjuvants in the context of tat- based vaccination and also providing a new promising candidate for genetic vaccine development. J. Cell. Physiol. 224: 702,709, 2010. © 2010 Wiley-Liss, Inc. [source] Expression of interferon-, subtypes in peripheral mononuclear cells from patients with chronic hepatitis C: a role for interferon-,5JOURNAL OF VIRAL HEPATITIS, Issue 2 2001E. Larrea Interferon (IFN)-, is a family of antiviral proteins encoded by different genes. The biological significance of the existence of various IFN-, subtypes is not clear. We have investigated the interferon system in chronic hepatitis C virus (HCV) infection, a disease that responds to interferon-,2 therapy in only a limited proportion of cases. We analysed the expression of interferon regulatory factor (IRF)-1, IRF-2, and IFN-, subtypes in nonstimulated and Sendai virus-stimulated peripheral blood mononuclear cells (PBMC) from HCV infected patients and healthy controls. We observed that the IRF-1 mRNA and IRF-1/IRF-2 ratios were increased in PBMC from hepatitis C patients with respect to normal subjects. Sendai virus stimulation of PBMC led to a significant increase in the levels of IRF-1, IRF-2 and IFN-, mRNAs and in the production of IFN-, protein with respect to basal values in healthy controls as well as in patients with HCV infection. In addition, we found that while natural HCV infection induced increased IFN-,5 expression in PBMC, in vitro infection of these cells with Sendai virus caused a raise in the expression of IFN-,8 in both patients and normal controls. In summary, our results indicate that virus-induced activation of the IFN system in human PBMC is associated with selective expression of individual IFN-, subtypes, IFN-,5 being the specific subtype induced in PBMC from patients with chronic HCV infection. [source] Association of neuropeptides with Th1/Th2 balance and allergic sensitization in childrenCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2006G. Herberth Summary Background Among neurogenic factors, the neuropeptides have an important regulatory influence on immune system activity and may lead to allergic sensitization. Objective The aim of our study was to investigate the relationship of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM) and substance P (SP) on modulation of Th1/Th2 balance and allergic sensitization in children. Methods Within the LISAplus (Life style,Immune system,Allergy) study, blood samples of 321 six-year-old children were analysed for concentration of neuropeptides, Th1 and Th2 cytokines, transcription factors for T cell regulation and suppressors of cytokine signalling. In addition, samples were screened for specific IgE against inhalant and food allergens. Results Children with high SOM values showed a Th2 polarization and a reduced expression of FOXP3, the marker for regulatory T cells. High (VIP) levels correlated inversely with the expression of T cell transcription factors (Tbet and SOCS3). In contrast, elevated levels of SP were associated with reduced GATA3 and SOCS3 expression and with increased IFN-, concentrations. Allergic sensitization was more prevalent in children with higher SOM and VIP concentrations but not associated with SP levels. Conclusion Our data reveal an association between neuropeptides and modulatory effects on immune cells in vivo, especially on Th1/Th2 balance with a correlation to allergic sensitization in children. We suggest that elevated SOM and VIP concentrations and the inducing factors should be considered as allergy risk factors. [source] Relationship between changes in interferon-, production by peripheral blood T cells and changes in peak expiratory flow rate in patients with chronic stable asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2002Y. I. Koh Summary Background Cytokines production by T helper lymphocytes (Th cells), which orchestrate the interplay of the different cells involved in airway inflammation of asthma, may be reflected in peripheral blood. Some studies have suggested that the Th cell cytokines by peripheral blood T cells correlate with asthma severity. Objective To investigate the relationship between changes in IFN-, production by peripheral blood T cells and changes in lung function in chronic stable asthmatics. Methods Sixteen patients with chronic stable moderate asthma aged 35,65 years (nine women) were recruited. Morning and evening peak expiratory flow rates (PEFR) monitoring and blood sampling for peripheral blood T cell culture, total IgE and blood eosinophils were performed at baseline and week 12. Levels of IFN-,, IL-4 and IL-5 in culture supernatants of peripheral blood T cell were determined by using enzyme-linked immunosorbent assay (ELISA) kits. Results Patients with increased IFN-, changes from baseline showed significantly increased changes in morning (P = 0.02) and evening (P < 0.05) PEFR compared with those with decreased IFN-, changes. The changes in IFN-, production and IFN-,: IL-4 ratio significantly correlated with the changes in morning PEFR (Rs = 0.59, P < 0.02; Rs = 0.63, P < 0.01, respectively) and tended to correlate with the changes in evening PEFR (Rs = 0.45, P = 0.08; Rs = 0.5, P = 0.05, respectively). The changes in IL-4 and IL-5 did not correlate with the changes in IgE and blood eosinophils, respectively. Conclusions These findings suggest that IFN-, may be associated with the alteration of lung function in asthmatics and play a role in the pathophysiology of chronic stable asthma. [source] Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasiaCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2007J. Visser Summary Oncogenic human papillomavirus (HPV)-infection is crucial for developing cervical cancer and its precursor lesions [cervical intraepithelial neoplasia (CIN)]. Regulatory T cells (Tregs) might be involved in the failure of the immune system to control the development of HPV-induced cancer. We investigated frequencies, phenotype and activity of Tregs in patients with cervical neoplasia. CIN and cervical cancer patients showed increased CD4+/CD25high T cell frequencies in peripheral blood and CD4+ T cell fraction. These CD4+/CD25high T cells represent Tregs as demonstrated by their low proliferation rate, low interferon (IFN)-,/interleukin (IL)-10 ratio, high expression of CD45RO, GITR, CTLA-4, forkhead box P3 (FoxP3) and low CD45RA expression. Moreover, in HPV16+ cervical cancer patients, in-vitro depletion of CD25+ T cells resulted in increased IFN-, T cell responses against HPV16 E6- and E7 peptides. Thus, increased frequencies of Tregs in cervical cancer patients may indeed suppress HPV-specific immunity. Longitudinal analysis of CD4+/CD25high T cell frequencies in patients showed a modest decline 1 year after curative surgery or chemoradiation. This study demonstrates increased frequencies and suppressive activity of Tregs in cervical cancer. These results imply that Tregs may suppress the immune control of cervical neoplasia and furthermore that suppression of immunity by Tregs will be another hurdle to overcome in therapeutic immunization strategies against cervical neoplasia. [source] Pamidronate infusion in patients with systemic sclerosis results in changes in blood mononuclear cell cytokine profilesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006L. D. Carbone Summary A single infusion of pamidronate was given to patients with systemic sclerosis (scleroderma, SSc) to assess effects on cytokine production by peripheral blood mononuclear cells (PBMC) and lymphocyte subsets. Eighteen patients with SSc received a single intravenous dose of 60 mg of pamidronate and were followed for 6 months. Assessment of cytokine production [interferon (IFN)-,, interleukin (IL)-10, transforming growth factor (TGF)-,1, tumour necrosis factor (TNF)-, and IL-4] by PBMC and lymphocyte subsets by flow cytometry was carried out before and after the pamidronate infusion. Unstimulated PBMC produced increased amounts of IFN-, and TNF-, and reduced levels of TGF-,1 for up to 24 weeks after the infusion. ,, T cells from patients with SSc were activated in vitro and produced increased IFN-,. The effects of pamidronate on modulation of cytokine profiles in patients with SSc may merit future study. [source] | ||||||||||