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IL-4 Secretion (il-4 + secretion)
Selected Abstracts22-ene-25-oxa-vitamin D: a new vitamin D analogue with profound immunosuppressive capacitiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2005C. Daniel Abstract Background, The biologic role of 1,25-dihydroxyvitamin D3, such as anti-inflammatory functions, reduction of cytokine production by T cells and immunoglobulin production by B cells, is well established. However, its clinical use as an immunosuppressive agent is limited because of the hypercalcemic toxicity occurring after systemic application. The purpose of this study was to investigate the immunmodulatory effects of 22-ene-25-oxa-vitamin D (ZK156979), a novel low calcemic vitamin D analogue. Materials and methods, Human peripheral blood mononuclear cells (PBMCs) from healthy donors were isolated using the Ficoll Hypaque technique, cultured for 24 h and treated with different concentrations of ZK156979 ranging from 10,5 to 10,10 mol L,1 compared with 1,25-dihydroxyvitamin D3[10,5,10,10 mol L,1] following phytohaemagglutinin (PHA) stimulation. Interferon gamma (IFN,), tumour necrosis factor alpha (TNF,), interleukin 1 beta (IL-1,), interleukin 10 (IL-10) and interleukin 4 (IL-4) secretion in supernatants were measured by ELISA. Results, ZK156979 inhibited the PHA-induced Th1-response (IFN, and TNF, levels) and the macrophage-product IL-1, in a concentration-dependent manner (10,10,10,5 mol L,1) with the efficiency on cytokine expression compared with 1,25-dihydroxyvitamin D3 being slightly reduced. In contrast, ZK156979 and 1,25-dihydroxyvitamin D3 both affected the Th2 response, leading to significantly increased IL-10- and IL-4 secretion. Conclusions, ZK156979 is a member of novel vitamin D analogues revealing prominent immunomodulatory and suppressive characteristics with distinctive inhibition of Th1-cytokines whereas the Th2 compartment is augmented, thus providing a considerable therapeutic potential in T-cell -mediated diseases. [source] Short-term dietary administration of celecoxib enhances the efficacy of tumor lysate-pulsed dendritic cell vaccines in treating murine breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 9 2006Tobias Hahn Abstract Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in the synthesis of prostaglandins. It is over-expressed in multiple cancers and has been associated with diminished tumor immunity. Dendritic cells (DCs) are considered candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC-based vaccines have exhibited minimal effectiveness against established tumors. In this study, we evaluated the effect of short-term administration of the selective COX-2 inhibitor celecoxib on the efficacy of DC-based vaccines in preventing and treating established 4T1 murine mammary tumors. We show that dietary celecoxib alone significantly suppresses the growth of primary tumors and the incidence of lung metastases in the prophylactic setting but is less effective against pre-established tumors. However, we demonstrate that celecoxib administered after primary tumor establishment synergizes with tumor lysate-pulsed DC and the adjuvant, GM-CSF, to improve the antitumor immune response by suppressing primary tumor growth and markedly reducing the occurrence of lung metastases. This triple combination therapy elicits a tumor-specific immune response evidenced by elevated IFN-, and IL-4 secretion by CD4+ T cells and results in increased infiltration of CD4+ and CD8+ T cells to the tumor site. In addition, dietary celecoxib inhibits angiogenesis evidenced by decreased vascular proliferation within the tumor and serum vascular endothelial growth factor levels. These studies suggest that short-term celecoxib therapy in combination with DC vaccines may be safely used for treating metastatic breast cancer. © 2005 Wiley-Liss, Inc. [source] Selective Th2 pattern of cytokine secretion in Mycobacterium avium subsp. paratuberculosis infected Crohn's diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2008Zhigang Ren Abstract Background and Aims:, The pathogenesis of Crohn's disease (CD) remains unclear. A major controversy has been whether infection with Mycobacterium avium subspecies paratuberculosis (MAP) plays a significant role. Current support for a role of MAP is largely based on epidemiological data. The aim of this study was to determine whether MAP detection in gut biopsies is associated with a different cytokine secretion profile as observed in whole blood culture. Methods:, A whole blood culture system was employed to measure cytokine secretion, using an ELISA assay, in subjects with CD (n = 46), ulcerative colitis (n = 30), irritable bowel syndrome (n = 22) and normal controls (n = 18). MAP status was defined by nested PCR using an IS900 sequence unique to MAP. Results:, Significantly higher levels of interleukin (IL)-4 (P < 0.05) and IL-2 (P < 0.05) were found in MAP+ CD compared to MAP, CD. This was selective, as MAP+ subjects in both normal and disease controls had similar levels of IL-4 and IL-2 to those with no detectable MAP. IL-4 secretion was correlated with IL-2 production in blood cultures in CD (P < 0.01), consistent with a skewed Th2 immune response. Conclusions:, This data set provides the first evidence of altered T cell function linked to MAP infection in CD, and provides a link between detection of MAP and disease. The pattern of cytokine shift in CD is consistent with the concept that the increasing incidence of CD is in part related to the hygiene theory. [source] Cellular responses to Loa loa experimental infection in mandrills (Mandrillus sphinx) vaccinated with irradiated infective larvaePARASITE IMMUNOLOGY, Issue 4 2000Ungeheuer In order to shed light on the mechanisms of antifilarial protective immunity, we investigated the course of experimental loaiosis after vaccination in a nonhuman primate host, Mandrillus sphinx. Six vaccinated (V) mandrills received 50 irradiated L3 while six nonvaccinated (NV) received saline solution on days ,60, ,30 and ,15. All animals were challenged with 100 intact L3 (day 0). Parasitological and immunological status were followed for 9 months. Vaccination delayed the appearance and mean peak of microfilaraemia. Five mandrills (Mf,) were never microfilaraemic (one V mandrill) or microfilaraemic on only one occasion (2 V and 2 NV), the other seven having stable microfilaraemia (Mf+). The cytokine response of peripheral blood mononuclear cells to L3 (L3 Ag) was Th2 dominated, while microfilariae (Mf Ag) elicited a Th0-like response. During vaccination, Th2 cytokine production significantly increased in V mandrills against L3 Ag, as well as Mf Ag, whereas Th1 cytokines decreased. On day 60 postinoculation, cellular proliferation was higher in V mandrills in response to L3 and Mf Ags and PHA-L mitogen. At the end of prepatency (on day 130), mandrills with delayed appearance of microfilaraemia exhibited a high, transient IL-2 and IL-4 secretion in response to L3 Ag. Finally, high anti-Mf Th2 cytokine levels characterized Mf,mandrills not only during prepatency, but also (for IL-5) before immunization. However, the presence of a balanced Th1 anti-L3 response during prepatency in the amicrofilaraemic mandrill suggests its importance in protective immunity. Taken together, our data suggest that Th2 cells and also Th1 components of the antifilarial response, especially to larval antigen, may contribute to parasite elimination. [source] Increased frequency of intracellular interleukin (IL)-13 and IL-10, but not IL-4, expressing CD4+ and CD8+ peripheral T cells of patients with atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2002M. Aleksza Summary Background A number of studies exist demonstrating the increased expression of type 2 cytokines and decreased capacity to produce interferon-, (IFN-,) in peripheral blood mononuclear cells (PBMCs) of patients with atopic dermatitis (AD). Objectives To clarify the results of recent studies concerning the role of interleukin (IL)-4 and IL-13 in PBMCs of AD patients, we analysed the activation status of lymphocyte subpopulations. Methods We measured the intracellular expression and serum levels of certain type 1 and type 2 cytokines, using cell surface and intracellular cytokine staining, flow cytometry and enzyme-linked immunosorbent assay techniques. Results The frequency of IL-10 and IL-13 producing CD4+ and CD8+ T cells was significantly higher in patients with AD, while the frequency of IFN-, secreting helper and cytotoxic T cells was significantly lower in patients with AD than in control subjects. The serum levels of IL-10 and IL-13 were also significantly increased. There were no significant differences observed between the experimental groups in the frequency of IL-4 producing CD4+ and CD8+ cells. Conclusions This study demonstrates a type 2 cytokine production in the CD4+ and CD8+ T cells of AD patients, which is characterized by an elevated IL-13, but not by IL-4 secretion, and by an increased level of the immunoregulatory IL-10, which can contribute to a decrease in IFN-, expression. [source] Effects of two novel cationic staphylococcal proteins (NP-taseand p70) and enterotoxin B on IgE synthesis and interleukin-4 and interferon-, production in patients with atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2000A. Jahreis We have characterized the cell-mediated and humoral immune response of patients with atopic dermatitis (AD) and healthy controls in response to two novel staphylococcal antigens (NP-tase, p70) and the superantigen staphylococcal enterotoxin B (SEB). The parameters studied were IgE, interleukin (IL)-4 and interferon (IFN)-, synthesis by peripheral blood mononuclear cells (PBMC) after stimulation with NP-tase, p70 and SEB in vitro. Both antigens, as well as SEB, induced IL-4 and IFN-, secretion in patients and controls. However, patients with AD showed a significantly diminished IFN-, production in response to NP-tase or SEB. Furthermore, we demonstrated a good correlation between antigen-stimulated IgE production and the IL-4/IFN-, ratio in vitro. A distinct subgroup of PBMC showed impaired IFN-, synthesis and enhanced IL-4 secretion after incubation with p70 or NP-tase. These data support evidence that a subgroup of patients with AD, synthesizing low levels of IFN-, after stimulation with staphylococcal antigens, may have impaired abilities to clear Staphylococcus aureus colonization. Persistent staphylococcal antigens could then be responsible for inflammatory and allergic skin reactions in patients with AD. We therefore conclude that, besides superantigens, staphylococcal antigens may also play a part in the pathogenesis of AD. [source] Novel B and T cell epitopes of chicken ovomucoid (Gal d 1) induce T cell secretion of IL-6, IL-13, and IFN-,CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2001E. Holen Background Chicken ovomucoid (OM, Gal d 1) has an important role in the pathogenesis of IgE-mediated allergic reactions to hen's egg white. Objectives The purpose of this study was to clarify the mechanisms of T cell recognition of ovomucoid using intact OM and chemically modified, characterized and homogeneous solid phase synthetic peptides covering the whole molecule. Methods Eighteen overlapping peptides were prepared by solid phase F-moc polyamide peptide synthesis (SPPS), characterized and high-pressure liquid chromatography (HPLC) purified. The peptides, together with intact, denatured and oxidized OM, were used to stimulate patient-derived cell cultures for mapping T cell epitopes. Proliferation responses, T cell phenotype and cytokine secretion using peripheral blood mononuclear cells (PBMC) from eight individuals and T cell lines (TCL) derived from six hen's egg-allergic patients, were examined. In addition, intact, denatured, oxidized and deglycosylated OM, as well as the peptides solely or with their keyhole limpet haemocyanin (KLH) complexes, were tested. For locating IgE and IgG B cell epitopes, seven egg-allergic patient sera and three OM-polyclonal sera were used. Healthy non-allergic individuals were included as controls. Results Seven peptides were recognized by specific IgE, while OM-specific TCL recognized 10 peptides. Six of the OM peptides were commonly recognized both by patient S-IgE and blood-derived TCL. Among those, one novel epitope, peptide OM 61,74, had the ability to bind IgE. Another peptide, OM 101,114, was recognized by IgE and IgG sera, but not by any of the TCLs. In contrast, the peptides OM 41,56, OM 71,84, OM 131,144 and OM 171,186 were exclusively T cell epitopes with no affinity to specific antibodies. Abundant TCL secretion of IFN-,, IL-6, IL-4, IL-13, IL-10 and TNF-, in response to OM stimulation indicates the contribution of Th2 as well as Th1/Th0 CD4+ cell subsets. For allergic patients moderate amounts of IFN-,, IL-13, and high amounts of IL-6, were secreted in response to TCL stimulation by OM peptides. High amounts of IL-6 were secreted in response to all molecular forms of OM (intact-, modified-OM and the peptides 71,84 and 51,64) when TCLs from two non-allergic donors were used. Conclusions One novel B cell epitope (OM 61,74) and 10 T cell epitopes have been identified. The most reactive epitopes of the OM molecule comprise the motifs 1,14 to 71,84, the overlapping peptide-pairs OM 121,134 and OM 131,144 and peptides OM 161,174 and 171,186. Peptides OM 1,14 and 171,186 are the only ones capable of inducing IL-4 secretion. Only one peptide (OM 11,24) induces IL-10 secretion. Those peptides recognized as both T and B cell epitopes or only T cell epitopes, have the potential to induce T cell secretion of moderate to high amounts of IL-13, IFN-, and particularly IL-6. [source] | ||||||||||