Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies with a murine model have shown that immunization with cryptococcal culture filtrate antigen (CneF) emulsified in complete Freund adjuvant (CFA) induces two populations of anticryptococcal reactive CD4+ T cells. One population (TDH cells) transfers anticryptococcal delayed-type hypersensitivity (DTH), and the other population (Tamp cells) amplifies the anticryptococcal DTH response of given to recipient mice at the time of immunization of the recipient. Treatment of mice with cyclosporin A (CsA) ablates the induction of Tamp cells but not TDH cells. The present study focused on assessing the cytokines produced by spleen cells taken from CsA-treated and control (solvent-treated) mice at days 1, 2, 4, and 6 after immunization. Supernatants from the spleen cells cultured in vitro for 24 or 48 h in medium alone or with CneF, concanavalin A, or phorbol 12-myristate 13-acetate plus calcium ionophore were assessed for the presence of interleukin-2 (IL-2), gamma interferon (IFN-gamma), IL-4, IL-5, and tumor necrosis factor. Spleen cells from CneF-CFA-treated mice produced IL-2 and IFN-gamma, but not IL-4 or IL-5, constitutively and in response to CneF, indicating that CneF-CFA induces a Th1 response. Tumor necrosis factor was not produced. Anticryptococcal TDH cells developed in spleens in which there were low levels of IFN-gamma and IL-2 (CsA-treated, immunized mice), whereas anticryptococcal Tamp cells along with TDH cells matured in spleens in which production of IFN-gamma and IL-2 was high (solvent-treated, immunized mice). The data also suggest that IL-2 and IFN-gamma produced by Tamp cells early after adoptive transfer are influential in the development of the amplified anticryptococcal DTH response that has been observed in Tamp cell-recipient mice.
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PMID:Cytokine profiles associated with induction of the anticryptococcal cell-mediated immune response. 840 74

Immunosuppression observed in chronic alcohol users is caused by multiple factors including the amount of alcohol consumed and alcohol-induced nutritional deficiencies. Investigators of the immunotoxic effects of ethanol (ETOH) frequently concentrate on the effects of ETOH and neglect nutrition as a confounding variable. This study investigated the immunotoxic effects of ETOH under variable dietary nutritional conditions. Mice were fed diets containing various levels of nutrients and ethanol for 7 weeks. Spleen cell number, and interleukin-2 and tumor necrosis factor (TNF) secretion were independent of the diet consumed, but were affected by consumption of ETOH. Body and spleen weights, and interferon-gamma secretion were modulated by ETOH as well as by diet. The results indicate that the nutritional composition of the diet consumed during concurrent administration of ETOH modulates the immunotoxic effects of chronic ETOH ingestion. We conclude that the levels of various nutrients in animal diets have to be planned and controlled carefully in order to identify directly the immunotoxic effects of ETOH.
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PMID:Role of nutrients in alcohol-induced immunomodulation. 847 Oct 91

A mouse model of spotted fever group rickettsiosis, in which disease results from disseminated rickettsial infection of endothelial cells and vascular damage, was developed by intravenous inoculation of 6- to 8-week-old, male, Balb/c mice with Rickettsia australis. Animals developed progressively severe vasculitis, interstitial pneumonia, and multifocal hepatic necrosis. These lesions correlated with early disseminated infection of endothelial cells followed by growth and invasion of rickettsiae into perivascular cells. The dose of 2 x 10(6) organisms was uniformly lethal. Serum interleukin- (IL) 1, IL-6, and interferon (IFN) increased by day 3 and tumor necrosis factor (TNF) on day 5. TNF, IL-6, and IFN declined on day 7. Spleen cells responded to Rickettsia australis antigen by producing IFN, TNF, IL-1, and IL-6 on day 5, followed by lower quantities of these cytokines on day 7. Despite the production of antibodies, IFN, TNF, IL-1, and IL-6, a lethal outcome occurred frequently. A decreased ability to secrete IL-2 suggests an element of infection-associated immunosuppression.
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PMID:Rickettsia australis infection: a murine model of a highly invasive vasculopathic rickettsiosis. 849 48

Using mice double deficient for tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha), we demonstrated that TNF and/or LT alpha are necessary for development of a normal splenic microarchitecture and for isotype switch after immunization with sheep red blood cells (SRBC). In the present study, we extended these observations by determining which TNF receptor (TNFR) is involved in morphological and functional differentiation of the spleen. Spleen morphology and antibody response were investigated in wild-type, TNFR1-/-, TNFR2-/- and TNF/LT alpha-/- mice immunized with SRBC. TNF/LT alpha-/- mice, which have a complete disruption of the TNF/LT alpha signaling system including the LT beta-receptor pathway, displayed an abnormal microarchitecture, and isotype switch did not take place. TNFR1-/- and TNFR2-/- mice displayed a normal spleen microarchitecture and mounted an IgM and IgG antibody response to SRBC. However, the IgG production in TNFR1-/- mice was minimal, with citers leveling off 6 d after immunization. In this strain, immunofluorescence revealed a lack of follicular dendritic cells (FDC) network, detected with FDC-M1 as well as anti-CR1, and a lack of germinal centers, detected with peanut agglutinin. In conclusion, whereas normal splenic microarchitecture and isotype switch might require the LT beta receptor, differentiation of FDC network, development of germinal centers, and full IgG response depend on signaling via TNFR1.
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PMID:Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling. 864 47

Using mice double deficient for tumor necrosis factor and lymphotoxin alpha (TNF/LT alpha-/-) we have demonstrated that TNF and/or LT alpha are important for morphogenesis of secondary lymphoid organs and for T-cell-dependent antibody responses. In the present study we attempted to identify the receptors involved in those functions of TNF and LT alpha. Spleen morphology and antibody responses were investigated in wild-type, TNFR1-/-, TNFR2-/-, and TNF/LT alpha-/- mice immunized with SRBC. TNF/LT alpha-/- mice, which have a complete disruption of the TNF/LT alpha signaling system including the lymphotoxin beta (LT beta) receptor pathway, displayed an abnormal splenic microarchitecture and isotype switch did not take place. TNFR1-/- and TNFR2-/- mice displayed a normal splenic morphology and mounted an IgM and IgG antibody response to SRBC. However, the IgG production in TNFR1-/- mice was abnormal, with titers leveling off after 6 days following primary immunization, and with a minimal response to a second antigen challenge. Immunofluorescence analysis of spleen sections revealed in this strain a lack of follicular dendritic cell (FDC) network and of germinal centers. In conclusion, while normal splenic microarchitecture and isotype switch might require the LT beta receptor, differentiation of the FDC network, development of germinal centers, a sustained IgG response, and probably the development of memory cells depend on signaling via TNFR1.
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PMID:Tumor necrosis factor receptor-1 signaling is required for differentiation of follicular dendritic cells, germinal center formation, and full antibody responses. 891 32

In the presence of interferon-gamma (IFN-gamma), human tumor necrosis factor-alpha (Hu-TNF-alpha), which binds to murine TNF-alpha receptor type 1 (TNF-R1) but not to murine TNF-R2, was effective in inducing nitric oxide (NO) production in spleen-derived macrophages (M phi), albeit at concentrations 12.5-fold greater than those required by murine TNF-alpha (Mu-TNF-alpha), to achieve the same result. Addition of anti-TNF-R1 completely inhibited the Mu-TNF-alpha-mediated induction of NO, demonstrating that TNF-R1 is critical to the IFN-gamma-dependent TNF-alpha-mediated induction of M phi effector function. However, treatment with anti-TNF-R2 resulted in a partial inhibition of M phi activation. Spleen-derived M phi were more dependent on TNF-R2 than RAW 264.7 or peritoneal M phi based on their responsiveness to Hu-TNF-alpha. Priming of spleen-derived M phi with either IFN-gamma or granulocyte-macrophage colony-stimulating factor (GM-CSF) heightened the maximal responses to both TNF-alpha species and increased the overall effectiveness of Hu-TNF-alpha without increasing expression of either TNF-alpha receptor. The dependence of spleen-derived M phi on both TNF-alpha receptors for signaling the induction of effector function supports an active signaling role for TNF-R2 in its synergy with TNF-R1 rather than a passive ligand passing role.
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PMID:Cytokine priming reduces dependence on TNF-R2 for TNF-alpha-mediated induction of macrophage nitric oxide generation. 897 9

Production of gamma-interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in Trypanosoma cruzi-infected mice results in the activation of inducible nitric oxide synthase (iNOS) and in elevated nitric oxide (NO) synthesis, which is important for the macrophage trypanocidal activity. However, NO has been shown to be involved in suppression of host immunity. In the present investigation, we studied the role of NO in inducing apoptosis in cells from BALB/c mice acutely infected by T. cruzi. Splenocytes from infected mice had a reduced cell viability and elevated levels of spontaneous apoptosis after 48 h in culture. Inhibition of NO production by the addition of the L-arginine analog NG-monomethyl-L-arginine (L-NMMA), or of monoclonal antibodies (mAbs) to IFN-gamma or TNF-alpha spleen cells, partially restored cell viability and caused a decrease in the levels of apoptosis in splenocytes from infected animals. Spleen cells from T. cruzi-infected mice had an apoptosis-specific pattern of internucleosomal DNA fragmentation which was most marked at the ninth day after infection when the plasma NO levels and parasitemia were increased. Treatment of infected mice with L-NMMA, anti-TNF-alpha, or anti-IFN-gamma mAbs caused reduction of both NO production and the amount of apoptotic cells, suggesting that NO plays a direct role in the induction of apoptosis in vivo. Taken together, these data support the hypothesis that, as well as modulating immunosuppression, NO produced by IFN-gamma and TNF-alpha activated macrophages plays a role in apoptosis induction during the acute phase of experimental T. cruzi infection.
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PMID:Nitric oxide-induced apoptotic cell death in the acute phase of Trypanosoma cruzi infection in mice. 976 73

Natural killer (NK) cells are thought to play an important role in the control of metastatic dissemination. Therefore, stimulation of cytotoxic activity of NK cells against neoplastic cells could be preventive for metastatic spread. Bomirski amelanotic (Ab) melanoma of Syrian hamster is a transplantable tumor metastasizing preferably to the kidneys. During growth of the melanoma a significant depression of cytotoxic activity of NK cells of tumor hosts is observed. Treatment of melanoma-bearing hamsters with indomethacin provided in drinking water resulted in the increase of NK cytotoxic activity of blood cells and in the lower occurrence of kidney metastasis. Spleen cells obtained from healthy and melanoma-bearing hamsters were cultured in vitro with agents influencing NK activity. We found an augmentative effect of human interleukin 2 (IL2) and human tumor necrosis factor (TNF). We also observed the synergistic effect of IL2/TNF combination, which was present in both groups of animals. The stimulatory effects of cytokines could be potentiated by the additional supplementation of cultures with indomethacin. Similar experiments were performed on spleen cells isolated from the healthy and tumor-bearing animals treated in vivo with indomethacin. Also, in this group of hamsters in vitro stimulation of NK cell activity by the cytokines was effective. The studies presented may give insight into the pathogenesis of immune abnormalities seen in advanced stages of progression of Ab melanoma, and can provide an experimental basis for immunomodulation in this tumor model of spontaneous metastasis.
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PMID:Indomethacin inhibits kidney metastasis in bomirski melanoma-bearing hamsters, and modulates natural killer cytotoxic activity of tumor hosts in vivo and in vitro. 985 38

5,6-Dimethylxanthenon-4-acetic acid (DMXAA) is a new antitumor drug currently undergoing clinical trial. Administration of DMXAA to mice with tumors leads to cessation of tumor blood flow and the onset of tumor hemorrhagic necrosis, accompanied by the production of the cytokine tumor necrosis factor (TNF). Previous studies have shown that DMXAA induces both tumor and host cells to synthesize TNF and that induced intratumoral TNF production correlates with the antitumor activity of DMXAA. To explore the hypothesis that TNF production by tumor cells contributed to the induction of hemorrhagic necrosis by DMXAA, TNF-/- (C57Bl/6 background) mice were used as recipients for the s.c. implantation of (TNF positive) colon 38 adenocarcinoma. Tumors removed 24 h after treatment with DMXAA (66 or 100 micromol/kg) were found to be hemorrhagic and necrotic. Cells expressing TNF mRNA in tumors removed 2 h after treatment with DMXAA (160 micromol/kg) were found by in situ hybridization to be comparable in frequency and distribution with those in tumors from C57Bl/6 TNF-positive mice. However, the amount of TNF protein extracted from tumors from TNF knockout mice was lower than that from TNF-positive mice. Spleen and liver tissue from TNF knockout mice, in contrast to that from TNF-positive mice, produced no TNF mRNA. TNF protein was undetectable in liver and spleen tissue from TNF knockout mice, but was evident in tissue from TNF-positive mice. These results confirm that DMXAA has the novel ability of inducing tumors to synthesize TNF in situ.
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PMID:Induction of intratumoral tumor necrosis factor (TNF) synthesis and hemorrhagic necrosis by 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF knockout mice. 1041 82

We evaluated the effect of cis-9, trans-11 (9c,11t) and trans-10, cis-12 (10t,12c) conjugated linoleic acid (CLA) on the immune system in C57BL/6J mice. Mice were fed experimental diets containing 0% CLA (controls), 1% 9c,11t-CLA, 1% 10t,12c-CLA or a 1:1 mixture (0.5% + 0.5%) of these two CLA isomers for 3 wk. Relative spleen weights of all CLA fed mice were greater than the controls. Spleen lymphocytes isolated from the mice fed 10t,12c-CLA produced more immunoglobulin (Ig)A and IgM but not IgG when stimulated with concanavalin A (ConA) compared with controls. IgA production from unstimulated spleen lymphocytes was greater in the 10t, 12c-CLA group than in controls. Conversely, 9c,11t-CLA did not affect the production of any of the Ig subclasses. Lymphocytes isolated from 9c,11t-CLA fed mice produced more tumor necrosis factor-alpha than the control group. The proportion of B cells in the spleen lymphocyte population was significantly lower in the 9c,11t-CLA group, and higher in the 10t,12c-CLA group than in the controls. Compared with the control group, the percentage of CD4(+) T cells was lower in the 10t,12c-CLA group, and the percentage of CD8(+) T cells was higher in the 9c,11t-CLA group. Furthermore, the percentage of CD8(+) T cells was higher in the 1:1 mixture group than in controls. The CD4(+)/CD8(+) ratio was lower in the 1:1 mixture group than in controls. These results suggest that 9c,11t and 10t,12c-CLA can stimulate different immunological effects and that the simultaneous intake of the two isomers can change the T cell population.
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PMID:Immunoglobulin and cytokine production from spleen lymphocytes is modulated in C57BL/6J mice by dietary cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid. 1261 53


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