Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0009319 (colitis)
 19,384 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 10 (IL-10) indirectly prevents antigen-specific T-cell activation, which is associated with downregulation of the antigen presentation and accessory cell functions of monocytes, macrophages, Langerhans cells and dendritic cells. In addition, IL-10 inhibits T-cell expansion by directly inhibiting IL-2 production by these cells. These properties of IL-10, together with its capacity to downregulate the production of proinflammatory cytokines and chemokines by activated monocytes, polymorphonuclear leucocytes and eosinophils, indicate that IL-10 is a potent immunosuppressant in vitro. IL-10 has similar activities in vivo. It inhibits lipopolysaccharide or staphylococcal enterotoxin B induced lethal shock in mice. In addition, IL-10 deficient mice develop chronic inflammatory bowel disease, which could be reduced, or prevented by IL-10 treatment. IL-10 also prevented the development of colitis in a SCID mouse model. Collectively, these data indicate that IL-10 has great potential therapeutical utility in the treatment of diseases, such as chronic inflammation, autoimmune diseases, transplant rejection, graft-versus-host disease and sepsis.
 ...
PMID:Immunosuppressive and anti-inflammatory properties of interleukin 10. 854 Oct 28

A T helper type 1 (Th1)-mediated colitis with similarities to inflammatory bowel disease in humans developed in severe combined immunodeficiency mice reconstituted with CD45RB(high) CD4+ splenic T cells and could be prevented by cotransfer of CD45RB(low) CD4+ T cells. Inhibition of this Th1 response by the CD45RB(low) T cell population could be reversed in vivo by an anti-transforming growth factor (TGF) beta antibody. Interleukin (IL) 4 was not required for either the differentiation of function of protective cells as CD45RB(low) CD4+ cells from IL-4-deficient mice were fully effective. These results identify a subpopulation of peripheral CD4+ cells and TGF-beta as critical components of the natural immune regulatory mechanism, which prevents the development of pathogenic Th1 responses in the gut, and suggests that this immunoregulatory population is distinct from Th2 cells.
 ...
PMID:A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells. 867 88

Administration of dextran sulfate to mice, given in the drinking water results in acute or subacute colonic inflammation, depending on the administration protocol. This colonic inflammation exhibits ulceration, healing and repair, and a therapeutic response that makes it valuable for the study of mechanisms that could act in the pathogenesis of human ulcerative colitis, a disease thought to have an immunologically dependent pathogenesis. To investigate if immunological mechanisms were involved in the induction of colonic inflammation in this model, mice with different degrees of immunodeficiency were used. It was shown that dextran sulfate induced colitis could be induced in Balb/c mice depleted of CD4(+) helper T cells by treatment with monoclonal antibodies preceded by adult thymectomy. The depletion of CD4(+) was verified by flow cytometric analysis. Furthermore, the colonic inflammation could equally be induced in athymic CD-1 nu/nu mice lacking thymus-derived T cells, in T and B-cell deficient SCID mice, and also in SCID mice depleted of NK cells by treatment with anti-asialo GM1 antibodies. The NK-cell depletion was verified by measuring spleen NK-cell activity. The resulting colonic inflammation in all these types of deficient mice was qualitatively comparable, as shown by clinical and histological appearance. These results indicate that the presence of functional T, B and NK cells is not crucial for the induction of dextran sulfate colitis in mice.
 ...
PMID:Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: effects in CD4(+) -cell depleted, athymic and NK-cell depleted SCID mice. 874 Oct 8

The above new findings concerning the immunological mechanisms governing mucosa, immune responses and oral tolerance in TCR-transgenic mice, as well as those operative in mice with experimental colitis, greatly expand our understanding of the processes that normally control mucosal inflammation and possibly other types of inflammation as well (Fig. 1). They indicate that, in the nondiseased mouse, ingested proteins evoke a Th1-cell (IFN-gamma) response in the mucosal follicles that is quickly counter-regulated by induction of T-cell anergy/deletion, if this Th1-cell response is inhibited (experimentally by anti-IL-12), TGF beta-producing cells appear, and these are capable of active immune suppression. This reciprocal relationship between IFN-gamma production and TGF-beta production is further supported in mouse models of mucosal inflammation. Thus, in the TNBS-colitis model, there is direct stimulation of the immune cells in the lamina propria as a result of diffuse haptenization of mucosal proteins, which leads to a massive Th1-cell response capable of overwhelming any suppressive counter-regulatory mechanisms normally generated in the PPs. This highly polarized Th1-cell response is controlled only by direct abrogation of IL-12 production with exogenous administration of anti-IL-12, or with indirect inhibition of this response via induction of oral tolerance and accompanying production of TGF-beta (Refs 6-8). The data obtained from this model are consistent with those obtained with another model of intestinal inflammation--inflammation in severe combined immunodeficiency (SCID) mice following lymphoid repletion with CD45Rbhi (naive) T cells. In this model, inflammation is again mediated by Th1 cells and is prevented by co-repletion with CD45Rbhi (memory) T cells, which appear to work by secreting TGF-beta (Refs 9, 10). Thus, a common feature of the various experimental models of intestinal inflammation studied to date is the Yin-Yang relationship of IFN-gamma and TGF-beta, with the former being proinflammatory and the latter anti-inflammatory. Is the IFN-gamma TGF-beta dichotomy that is evident both in the normal state and in models of inflammation simply a reflection of an underlying Th1 Th2 dichotomy? The answer to this important question is not yet known. Thus, while it is clear from the in vitro studies already discussed that IL-12 and/or IFN-gamma inhibit TGF-beta production, the role of IL-4 in this process is more elusive. These in vitro studies indicate that IL-4 is not required for TGF-beta production, a finding that is consistent with studies in which the transfer of CD45Rbhi, T cells from IL-4-/- mice protected SCID mice from colitis induced by CD45Rbhi T cells. However, the addition of IL-4 to in vitro cultures containing anti-IL-12 augmented TGF-beta production, most probably by IL-4 acting as a growth factor for TGF-beta-producing cells rather than as an inducing factor (T. Marth et al., unpublished). Obviously, more work will be necessary to resolve this issue. Finally, it should be noted that the above considerations apply to human inflammatory diseases of the gastrointestinal tract, such as Crohn's disease. Recently, it has been shown that T cells extracted from Crohn's disease tissues manifest skewed Th1-cell responses. The hypothesis can therefore be put forward that this disease results from a dysregulated Th1-cell response to ubiquitous mucosal antigens that is not appropriately controlled by normal counter-regulatory mechanisms. Interventions that artificially bring the excessive Th1-cell response back into balance, such as administration of IL-12 antagonists, should therefore find a central place in the treatment of the disease.
 ...
PMID:Reciprocal IFN-gamma and TGF-beta responses regulate the occurrence of mucosal inflammation. 905 54

Transfer of specific T lymphocyte subsets isolated from the spleens of healthy donor mice into immunodeficient SCID mice leads to chronic intestinal inflammation with characteristics similar to those of human inflammatory bowel disease (IBD). CD4+, CD45RBhigh cells cause disease, whereas CD4+, CD45RBlow and CD8+, CD45RBhigh cells do not. Despite this difference, we demonstrate that all three T cell populations reconstitute the intraepithelial and lamina propria compartments of both small and large intestines of SCID recipients. Therefore, infiltration of lymphocytes alone is not sufficient for disease development. CD4+ lymphocytes that have trafficked to the SCID intestine exhibit a phenotype characteristic of normal mucosal lymphocytes. This includes high expression of alpha E integrin and CD69, expression of CD8 alpha alpha homodimers in some of the intraepithelial lymphocytes, as well as low expression of CD62L and CD45RB. The phenotype of the infiltrating mucosal cells is indistinguishable, with respect to the cell surface markers tested, regardless of whether the starting donor population is CD45RBhigh or CD45RBlow. Severe inflammation is restricted primarily to the colon despite lymphocyte infiltration throughout the length of the intestine. This suggests that some property of the colon microenvironment contributes to inflammation. Consistent with this, transfer of CD4+, CD45RBhigh cells to SCID mice that have significantly reduced numbers of enteric flora results in attenuation of the wasting and colitis. Fewer numbers of donor lymphocytes are recovered from the intraepithelial and lamina propria compartments of reduced flora SCID mice. We hypothesize that the ability of pathogenic cells to traffic to the intestine and mediate colitis may be driven by T cell reactivity to bacteria or bacterial products.
 ...
PMID:Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RBhigh T cells to SCID recipients. 912 Mar 8

Forty two infants below the age of 2 years presenting with chronic non-infective diarrhoea and shown to have histologically proved colitis were investigated over a five year period. Allergic colitis was the most common cause of colitis, accounting for 62% of the cases. Other colitides diagnosed included: non-specific colitis, autoimmune enterocolitis, and ulcerative colitis accounting for 10% each; severe combined immunodeficiency 7%, and Crohn's disease 3%. A positive family history and a personal history of atopy were obtained in 48% and 29% of the cases respectively. Serum immunoglobulin A, IgG2, and IgG4 were very low in over 50% of the entire cohort of infants with colitis; 66% of those with severe combined immunodeficiency, autoimmune enterocolitis, and ulcerative colitis (n = 11) had low CD3 and CD4 T lymphocytes with an accompanying increase in CD8 in two thirds of those with severe combined immunodeficiency. T lymphocytes were normal in those with allergic colitis. Thus infants with proved non-infective colitis as a group show a high prevalence of IgA, IgG2, and IgG4 deficiency. It is likely that this minor deficiency of mucosa associated immunoglobulin production has a role in the pathogenesis of the colitic process.
 ...
PMID:Non-infective colitis in infancy: evidence in favour of minor immunodeficiency in its pathogenesis. 916 29

Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad array of immune parameters including T helper cell type 1 (Th1) cytokine production, antigen presentation, and antigen-specific T cell proliferation. To understand the consequences of altered expression of IL-10 in immune models of autoimmune disease, the response to infectious agents, and the response to tumors, we developed transgenic mice expressing IL-10 under the control of the IL-2 promoter. Upon in vitro stimulation, spleen cells from unimmunized transgenic mice secrete higher levels of IL-10 and lower amounts of IFN-gamma than do controls, although no gross abnormalities were detected in lymphocyte populations or serum Ig levels. Transfer of normally pathogenic CD4(+) CD45RBhigh splenic T cells from IL-10 transgenic mice did not cause colitis in recipient severe combined immunodeficiency mice. Furthermore, co-transfer of these transgenic cells with CD4(+) CD45RBhigh T cells from control mice prevented disease. Transgenic mice retained their resistance to Leishmania major infection, indicating that their cell-mediated immune responses were not globally suppressed. Lastly, in comparison to controls, IL-10 transgenic mice were unable to limit the growth of immunogenic tumors. Administration of blocking IL-10 mAbs restored in vivo antitumor responses in the transgenic mice. These results demonstrate that a single alteration in the T cell cytokine profile can lead to dramatic changes in immune responses in a manner that is stimulus dependent. These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10.
 ...
PMID:Altered immune responses in interleukin 10 transgenic mice. 918 82

Forty two infants below the age of two years presenting with chronic non infective diarrhoea and shown to have histologically proven colitis were investigated over a five year period at this hospital. Allergic colitis was the most common cause of colitis accounting for sixty two percent of the cases. Other colitides diagnosed included: non specific colitis, autoimmune enterocolitis and ulcerative colitis accounting for 9.5% each, severe combined immunodeficiency 7.1% and Crohn's disease 2.8%. A positive family history and a personal history of atopy was obtained in 47.6% and 28.6% of the cases. Serum immunoglobulin A, IgG2 and IgG4 were very low in over 50% of the infants with colitis. Sixty six percent of those with severe combined immunodeficiency, autoimmune enterocolitis and ulcerative colitis (n = 11) had low CD3 and CD4 T lymphocytes with an accompanying elevated CD8 in 2/3 of those with severe combined immunodeficiency. T lymphocytes were normal in those with allergic colitis. We conclude that infants with proven non infective colitis show as a group a high prevalence of IgA, IgG2 and IgG4 deficiency. It is likely that this minor deficiency of mucosal associated immunoglobulin production have a role in the pathogenesis of the colitic process.
 ...
PMID:Non infective colitis in infancy: evidence in favour of minor immunodeficiency in its pathogenesis. 929 24

Induction and maintenance of peripheral tolerance are important mechanisms to maintain the balance of the immune system. In addition to the deletion of T cells and their failure to respond in certain circumstances, active suppression mediated by T cells or T-cell factors has been proposed as a mechanism for maintaining peripheral tolerance. However, the inability to isolate and clone regulatory T cells involved in antigen-specific inhibition of immune responses has made it difficult to understand the mechanisms underlying such active suppression. Here we show that chronic activation of both human and murine CD4+ T cells in the presence of interleukin (IL)-10 gives rise to CD4+ T-cell clones with low proliferative capacity, producing high levels of IL-10, low levels of IL-2 and no IL-4. These antigen-specific T-cell clones suppress the proliferation of CD4+ T cells in response to antigen, and prevent colitis induced in SCID mice by pathogenic CD4+CD45RB(high) splenic T cells. Thus IL-10 drives the generation of a CD4+ T-cell subset, designated T regulatory cells 1 (Tr1), which suppresses antigen-specific immune responses and actively downregulates a pathological immune response in vivo.
 ...
PMID:A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. 933 86

Induction and maintenance of peripheral tolerance are important mechanisms to maintain the balance of the immune system. In addition to the deletion of T cells and their failure to respond in certain circumstances, active suppression mediated by T cells or T-cell factors has been proposed as a mechanism for maintaining peripheral tolerance. However, the inability to isolate and clone regulatory T cells involved in antigen-specific inhibition of immune responses has made it difficult to understand the mechanisms underlying such suppression. Here, we show that chronic activation of both human and murine CD4+ T cells in the presence of interleukin (IL)-10 gives rise to CD4+ T-cell clones with low proliferative capacity, producing high levels of IL-10, low levels of IL-2 and no IL-4. These antigen-specific T-cell clones suppress the proliferation of CD4+ T cells in response to antigen, and prevent colitis induced in SCID mice by pathogenic CD4+CD45RBhigh splenic T cells. Thus IL-10 drives the generation of a CD4+ T-cell subset, designated T regulatory cells 1 (Tr1), which suppresses antigen-specific immune responses and actively downregulates a pathological immune response in vivo.
 ...
PMID:Interleukin 10 is a growth factor for a population of regulatory T cells. 953 36


1 2 3 4 5 6 7 8 9 10 Next >>