Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Haemophilus influenzae type b polysaccharide-conjugate vaccines elicit protective antibody responses in young infants. One of these conjugates, polysaccharide linked to outer membrane protein complex (PRP-OMPC), is produced by linking the capsular polysaccharide to an outer membrane protein complex derived from group B Neisseria meningitidis. The outer membrane protein complex contains T cell carrier epitopes that elicit T cell-dependent antibody responses. OMPC also has been shown to increase the antibody response to other proteins administered concurrently that are not covalently linked (i.e., acts as an adjuvant). In this study PRP-OMPC immunized mice demonstrated significant increases in spleen size as well as in splenocyte number as compared to saline controls (p < 0.01, p < 0.001, respectively). No such increase was noted after immunization with another H. influenzae type b-conjugate vaccine, oligosaccharide linked to a variant of diphtheria toxin. By analytic flow cytometry, the mice immunized with PRP-OMPC demonstrated an increase in large splenocytes expressing the Ag Mac-1 (CD11b, CR3). Furthermore, the spleens on histologic examination were characterized by an increase in the red pulp area consisting predominantly of cells of macrophage morphology. By immunohistochemical staining, the cells were identified as macrophages due to expression of Mac-1 and p150,95 (CD11C) Ag. After PRP-OMPC immunization, severe combined immunodeficient mice also demonstrated significant splenomegaly with an increase in macrophages identified by expression of Mac-1 and MHC class II Ag. Thus PRP-OMPC vaccine resulted in T cell-independent splenomegaly with an increase number of macrophages. We propose that this unique property may confer increased immunogenicity to PRP-OMPC through macrophage activation and cytokine release. Furthermore, the effect on macrophages may explain the "adjuvant" capacity of OMPC.
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PMID:Effect of Haemophilus influenzae polysaccharide outer membrane protein complex conjugate vaccine on macrophages. 146 Feb 86

The toxic oil syndrome is characterized by IgE elevation and eosinophilia, as well as scleroderma-like skin manifestations and other symptoms of autoimmune disease. Fatty acid anilides, found in large amounts in adulterated cooking oil, were suspected to be the etiologic agent in this disease. The capacity of oleic acid anilide to induce features of autoimmunity in vivo was investigated. B10.S mice were continuously treated i.p. with oleic acid anilide for 6 wk by using osmotic pumps. A significant increase in IgE and IgM serum levels was observed after 1 to 3 wk; subsequently five of six mice developed IgG1 levels 3.5- to 10-fold higher than the controls. Anilide-treated mice developed splenomegaly with a 2.1- and a 3.5-fold increase in IgM- and IgG-bearing splenocytes, respectively, and a 5.6- and 29-fold elevation in functional IgM- and IgG-secreting cells, respectively. Increased serum levels of predominantly IgM antibodies to histone, denatured DNA, and DNP as well as rheumatoid factor were detected. In vivo expression in the spleen of 10 cytokine genes was also examined, and mRNA encoding IL-1 beta and IL-6 were significantly elevated in splenocytes of anilide-treated mice. The enhanced Ig production suggests that anilide induced a cytokine-mediated polyclonal activation of B cells. Elicitation of IgM antibodies to denatured forms of autoantigens indicates that anilide treatment partially broke autoimmune tolerance in these mice. Anilide-treated mice may be a useful animal model for further exploring the mechanism and pathogenesis of systemic autoimmunity in the toxic oil syndrome.
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PMID:Isotype-restricted hyperimmunity in a murine model of the toxic oil syndrome. 158 38

Human proto- and metazoa, which spend a part of their life-cycle within erythrocytes or extracellularly in human blood or in monocyte-derived macrophages, are considered as blood parasites. In spite of their individually widely differing habitat, they elicit a common hematological syndrome essentially consisting in hemolytic anemia and splenomegaly. Furthermore, some basic factors of host/parasite interaction are very similar: (1) Specific cell attachment through receptor/ligand mechanisms such as the integrin/RGD-oligopeptide system, (2) competition for essential nutrients such as iron, which may be influenced therapeutically to the disadvantage of the parasite by the use of iron chelators, and (3) provocation of host defense through T-cell dependent, cytokine-mediated macrophage activation.
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PMID:[Blood parasitosis--mechanisms and limitations of a species-alien coexistence]. 195 40

Interleukin 6 (IL-6) is an important regulator of the acute phase response, T cell function, and terminal B cell differentiation. Excessive or inappropriate production of this cytokine may be involved in a variety of autoimmune and neoplastic disorders. To investigate the consequences of dysregulated synthesis of IL-6 in vivo, a high-titer recombinant retroviral vector produced in psi-2 packaging cells was used to introduce the coding sequences of murine IL-6 into mouse hematopoietic cells. Congenitally anemic W/Wv mice reconstituted with bone marrow cells transduced with the retroviral vector developed a syndrome characterized by anemia, transient granulocytosis, hypoalbuminemia, and polyclonal hypergammaglobulinemia, with marked splenomegaly and peripheral lymphadenopathy. Extensive plasma cell infiltration of lymph nodes, spleen, liver, and lung was noted. The similarity of these findings to those of multicentric Castleman's disease, taken together with the observation that lymph nodes from these patients elaborate large amounts of this cytokine, suggest that the inappropriate synthesis of IL-6 has a primary role in the pathogenesis of this systemic lymphoproliferative disorder.
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PMID:Dysregulated interleukin 6 expression produces a syndrome resembling Castleman's disease in mice. 238 5

The effects of the in vivo administration of interleukin 1 (IL 1) on lymphocytes from lymph node and spleen were analyzed. Mice received five daily subcutaneous (s.c.) injections of various doses of human recombinant IL 1 beta. Either 1 or 7 days after IL 1 treatment, spleens, popliteal and inguinal lymph nodes were collected. Lymphadenosis and splenomegaly were observed in the IL 1-treated animals. Lymph nodes from IL 1-treated mice contained a higher percentage of B cells than controls, and B cells from IL 1-treated mice expressed dramatically increased levels of Ia antigen. Lymphadenosis and splenomegaly, as well as the changes in subset distributions and Ia expression were transient. Concomitant treatment of mice with IL 1 and anti-IL 4 monoclonal antibody suppressed IL 1 effects on B cell Ia expression, but not on the B/T cell ratio. In situ hybridization analyses revealed that IL 1 treatment induced the expression of mRNA for IL 4, interferon-gamma, and IL 2 in lymph node and spleen cells. The distribution of cells expressing the various cytokine mRNA was markedly different between the spleens and lymph nodes.
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PMID:In vivo administration of interleukin 1 elicits increased Ia antigen expression on B cells through the induction of interleukin 4. 257 31

Three cases of a syndrome featuring massive splenomegaly, gross generalized lymphadenopathy, and moderate hepatomegaly are reported. Spleen weights ranged from 800 to 2400 g. Gradual depletion of lymphoid germinal centers, and prominent infiltration of the splenic and lymph node cords with plasma cells, immunoblasts and actively dividing B cells were the most distinctive histological features. The liver in two cases showed portal infiltrates. A marked hypergammaglobulinemia, a decrease in blood cholesterol level and hematological abnormalities related to hypersplenism were observed. The condition begins early in life and runs a chronic course, of up to 25 years. There was a family history in only one instance. Since there was no generalized immunodeficiency nor local depletion of T cells or dendritic reticulum cells, a failure in the local regulation of the immune response and possible cytokine production is postulated. This condition underlines the pivotal role of the local organization of the germinal centers in cellular cooperation and in the carrying out and regulation of the immune response.
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PMID:The disappearance of germinal centers in chronic lymphadeno-hepato-splenomegaly syndrome in childhood: report of three cases. 271 99

IL-1 has been shown to stimulate the release of granulocyte-macrophage CSF, granulocyte-CSF, and macrophage-CSF from "accessory cell populations" in vitro, and it stimulates the appearance of colony-stimulating activity in the sera of mice in vivo. This cytokine has also been proposed to act on primitive hematopoietic progenitor cells to stimulate expression of receptors for the CSF. We sought to determine whether IL-1 beta could influence platelet and/or megakaryocytes and their progenitor cells following in vivo administration to normal mice. Our results demonstrated that, although administration of IL-1 beta clearly expands the pool of megakaryocyte-CFU and acetylcholinesterase-positive megakaryocytic cells (primarily in the spleen), it causes a transient and dose-dependent reduction of circulating platelets. The associated thrombocytopenia can be abolished by splenectomy before IL-1 beta administration, and is not temporally associated with the development of splenomegaly.
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PMID:Alterations in megakaryocyte and platelet compartments following in vivo IL-1 beta administration to normal mice. 278 31

Murine retrovirus infection induces loss of vitamin E and immune dysfunction with loss of cytokine production by T-helper cells. Therefore interferon-gamma (IFN-gamma) was given during dietary vitamin E supplementation to effectively prevent murine retrovirus-induced immunosuppression, cytokine dysregulation, and development of murine AIDS. Administration of IFN-gamma during vitamin E supplementation significantly prevented development of retrovirus-induced suppression of splenic natural killer cell activity and T cell proliferation. It also significantly slowed retrovirus-induced elevation of T helper (Th) 2 cytokine [interleukin (IL)-4, IL-5, and IL-10] production and monokine (IL-6 and tumor necrosis factor-alpha) secretion by splenocytes. The treatment also prevented loss of Th1 cytokine (IL-2 and IFN-gamma) secretion by splenocytes from retrovirus-infected mice alleviating splenomegaly and hypergammaglobulinemia. The combined therapy had an additive therapeutic impact. It was more effective than IFN-gamma treatment or vitamin E supplementation alone in delaying the development of retrovirus-induced immunosuppression with its cytokine dysregulation.
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PMID:Vitamin E supplementation with interferon-gamma administration retards immune dysfunction during murine retrovirus infection. 749 68

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS which is functionally similar to human AIDS. Dietary supplementation, with a 15-, 150- and 450-fold increase of vitamin E in a liquid diet, significantly restored levels of interleukin-2 (IL) and interferon-gamma produced by splenocytes, which were suppressed by retrovirus infection. Retrovirus infection elevated levels of IL-6 and IL-10 produced by splenocytes, which were significantly normalized by all levels of vitamin E supplementation, respectively. Increased levels of IL-6 and tumor necrosis factor-alpha, produced by splenocytes during progression to murine AIDS, were also significantly normalized by all levels of vitamin E supplementation. Vitamin E supplementation restored retrovirus-suppressed splenocyte proliferation and natural killer cell cytotoxicity. Vitamin E supplementation also alleviated the AIDS symptoms: splenomegaly and hypergammaglobulinemia. These data indicate that dietary vitamin E supplementation at extremely high levels was not immunotoxic, and can modulate cytokine release and normalize immune dysfunctions during progression to murine AIDS. It should favorably affect host resistance and thereby retard the development of AIDS.
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PMID:Modulation of immune function and cytokine production by various levels of vitamin E supplementation during murine AIDS. 762 53

The majority of biologic functions assigned to cytokines have been characterized by in vitro assay systems which may not necessarily reflect cytokine roles in vivo. Recently, recombinant virus approaches have allowed tissue-specific expression of foreign gene products in experimental animal models. We have constructed recombinant human type 5 adenoviruses, deficient in the E3 region of the genome, with incorporated rodent IL-6 cDNA that express significant levels of biologically active IL-6 on infection both in vitro and in vivo. After i.p. injection, the liver, spleen, and peritoneum appear to be primary sites of expression, whereas the lung and bronchus are the main sites of expression after intratracheal instillation. Injection i.p. of BALB/c mice with the murine rIL-6 virus causes an increase in serum levels of bioactive IL-6 for up to 6 days post-infection, whereas similar changes are not seen in animals infected with control viruses. Coincident with enhanced plasma levels of IL-6, we detect raised serum levels of hepatic-derived acute phase proteins. Associated with the expression of IL-6 in the liver and spleen, at 7 days we note a fourfold splenomegaly with expansion of B and T cell compartments, as well as the presence of lymphoid aggregates in the liver. These morphologic changes had resolved by 16 days. Our findings demonstrate that recombinant human type 5 adenoviruses expressing cDNA for various cytokines could be used as a transient pseudo-transgenic animal model to investigate the biologic function of cytokines in vivo.
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PMID:Construction of recombinant human type 5 adenoviruses expressing rodent IL-6 genes. An approach to investigate in vivo cytokine function. 769 5


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