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

Heat- or merthiolate-inactivated Trypanosoma equiperdum was administered to recipient mice that were subsequently challenged with viable inocula of the same stabilate. Only mice inoculated with merthiolate-killed parasites were completely protected from a challenge inoculum of 10(3) trypanosomes, an effect that was abolished by prior immunosuppression of mice. Immune sera from protected animals contained high levels of interferon (IFN)-gamma and specific IgG2a antibodies. Spleen cells from these mice produced high amounts of interleukin (IL)-2 and IFN-gamma in vitro in response to specific antigen or concanavalin A, whereas splenocytes from mice receiving heat-killed parasites produced high amounts of IL-6. In contrast, the production of tumor necrosis factor (TNF)-alpha and colony-stimulating activity (CSA) was not significantly different in mice receiving either killed parasite preparation. The protection in immunized mice was associated with the detection of strong delayed-type hypersensitivity (DTH) to T. equiperdum antigens, an effect that could be adoptively transferred onto naive recipients by specifically immune CD4+ lymphocytes. These results suggest that the development of protective immunity in mice to T. equiperdum by our immunization protocol may involve the activity of helper/DTH T cells, particularly those of the Th1 subset.
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PMID:Involvement of the Th1 subset of CD4+ T cells in acquired immunity to mouse infection with Trypanosoma equiperdum. 135 13

The relationships between metabolic alterations and tissue-specific gene expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), gamma-interferon (gamma-IFN), and interleukin 1 and serum levels of TNF-alpha and IL-6 before and after a live Escherichia coli septic challenge to rats were examined. From 0 to 2 h, serum glucose significantly decreased while plasma glucagon increased. By 8 h, plasma glucagon, serum insulin, and glucose appearance were significantly elevated. Gene expression of phosphoenolpyruvate carboxykinase increased 1 h after E. coli but by 4 h was significantly decreased. TNF-alpha mRNA (liver and spleen) and serum peptide levels peaked 1-2 h after the septic challenge and then decreased substantially by 6-8 h. Spleen IL-6 and gamma-IFN mRNA expression reached a maximum 4 h after E. coli challenge, whereas serum IL-6 levels were elevated by 2 h after injection of the bacteria. The increase in TNF-alpha mRNA and serum peptide levels correlated with the early fall in serum glucose and rise in plasma glucagon. Alterations in the rate of glucose appearance and plasma glucagon were observed later and coincided with the increased mRNA expression of IL-6 and gamma-IFN. Thus the metabolic alterations observed in the septic rat are associated with a complex cascade of several cytokines.
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PMID:Sepsis-induced cascade of cytokine mRNA expression: correlation with metabolic changes. 159 Mar 83

Cryosurgery provides two prominent features, that is in situ destruction of malignant tumor and potential immunotherapy against tumor. In order to investigate the immunological response after cryosurgery, immunological system of macrophage activation were studied in an experimental tumor system using BALB/c mice and syngeneic Meth-A fibrosarcoma. The mice inoculated the cryodestroyed Meth-A (Cryo-Meth-A mice) acquired antitumor potency in Meth-A challenge test, and the mice inoculated the Mitomycin C treated Meth-A (MMC-Meth-A mice) also acquired antitumor potency. Spleen cells of Cryo-Meth-A mice showed antitumor activity in Winn assay, and spleen cells of MMC-Meth-A mice also showed antitumor activity. The effector cells in Cryo-Meth-A mice were mainly macrophages and natural killer (NK) cells. On the other hand, they were mainly macrophages and cytotoxic T lymphocytes (CTL) in MMC-Meth-A mice. The maximum macrophage cytostatic activity of Cryo-Meth-A mice was noted on 14 days after inoculation (Day 14), whereas it appeared on Day 7 and continued until Day 14 in MMC-Meth-A mice. Macrophages of Cryo-Meth-A mice enhanced the production activity of interleukin 1 (IL-1), interferon (IFN) and prostaglandin E2 (PGE2). On the other hand, macrophages of MMC-Meth-A mice enhanced production activity of tumor necrosis factor (TNF) and increased Ia antigen positive ratio. These findings suggest that macrophages of both groups are activated by different immunological mechanisms. It was found that Cryo-Meth-A played a role as an alpha-IFN inducer, and the macrophages stimulated with Cryo-Meth-A produced alpha-IFN in vitro. Intraperitoneal (i.p.) administration of the anti-alpha-IFN antibody carried down-regulation of macrophage cytostatic activity and NK activity of Cryo-Meth-A mice, whereas MMC-Meth-A mice were not. In addition to these findings, CTL activity enhanced some extent by i.p. administration of the anti-alpha-IFN antibody. These facts suggest that the alpha-IFN have two ways of immunological regulation, the first one is the activation of macrophage cytostatic activity and NK activity, and the other is down-regulation of CTL activity by suppression of Ia antigen expression of macrophages. These results suggest that cryodestruction changes the tumor antigen of Meth-A cells, thereby Cryo-Meth-A induces peculiar immunological response.
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PMID:[Activation and regulation of macrophages induced by inoculation of cryodestroyed tumor cells]. 213 4

In order to clarify the effect of recombinant human tumor necrosis factor (rHu-TNF) on the antitumor T cell immune response, we examined the effect of rHu-TNF on the generation of cytotoxic T cells (CTL) against syngeneic tumor cells. Spleen cells from X5563 plasmacytoma-transplanted mice were stimulated in vitro with mitomycin C-treated X5563 cells in the presence or absence of rHu-TNF. The generation of CTL was augmented in a dose-dependent manner by the addition of rHu-TNF. The augmenting effect of rHu-TNF was more marked when indomethacin was added to the culture. The augmenting effect was observed only when rHu-TNF was added at the early stage of the generation of CTL. The cell surface phenotype of CTL generated was L3T4- and Lyt2+. The augmentation was shown not only by the chromium-51 release assay but also by the Winn assay. As to the specificity, the augmentation of CTL generation was observed by the addition of rHu-TNF when responder-primed spleen cells were stimulated with the tumor cells in vitro. On the other hand, augmentation was not observed when responder spleen cells were not stimulated with the tumor cells in vitro, or when responder spleen cells were obtained from normal mice. The CTL generated was not cytotoxic against other tumor cells of the same haplotype. Thus, rHu-TNF augmented the generation of CTL against syngeneic tumor cells in an antigen-specific manner. The in vivo effect of rHu-TNF was examined by administering rHu-TNF into X5563-bearing mice. The spleen cells of rHu-TNF-injected mice generated a much higher CTL activity against X5563 cells in vitro than did the spleen cells of uninjected mice. From these results, a possibility can be considered that in some cases, rHu-TNF may exert its antitumor activity by stimulating the immune system.
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PMID:Augmentation of the generation of cytotoxic T lymphocytes against syngeneic tumor cells by recombinant human tumor necrosis factor. 264 56

Spleen cells treated with mitogens produce a potent bone-resorbing factor called osteoclast-activating factor (OAF). To examine the relationship between the bone-resorbing factor and other protein factors produced by spleen cells, the colony-stimulating factor (CSF), the differentiation-inducing factor (DIF), the macrophage fusion factor (MFF), and the macrophage growth factor (MGF) were purified from 2.68 liters of conditioned medium of mouse spleen cell cultures treated with concanavalin A. Purification was performed successively by DEAE-cellulose, Blue Sepharose, and Sephadex G-150 column chromatography and high-pressure liquid chromatography (HPLC). The DIF was successfully separated from CSF and MGF on HPLC. CSF coincided with MGF on HPLC, but MFF disappeared before application to HPLC. Only the DIF exhibited bone-resorbing activity, whereas CSF and MGF did not. The DIFs purified from L929 cells and Ehrlich ascites tumors similarly exhibited bone-resorbing activity. The DIFs purified from spleen cells and Ehrlich ascites tumor cells exhibited neither interleukin 1 (IL-1) activity nor tumor necrosis factor (TNF) activity, though the unfractionated conditioned medium from spleen cells did exhibit them. In the light of recent reports that IL-1 beta and TNF also stimulate bone resorption, the term OAF should refer to a generic activity rather than a single factor.
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PMID:Differentiation-inducing factor purified from conditioned medium of mitogen-treated spleen cell cultures stimulates bone resorption. 346 68

Guanine ribonucleosides with single substitutions at the C8 position (monosubstituted) or with dual substitutions at the C8 and N7 positions (disubstituted) up-regulate a spectrum of immunologic responses, including cytolytic responses to tumor cells. The current studies were undertaken to determine the effects of dual substitution on a number of nucleoside-inducible immunological parameters. To do so, two monosubstituted analogues, 8-bromoguanosine and 8-mercaptoguanosine, were directly compared with two disubstituted analogues, 7-methyl-8-oxoguanosine and 7-allyl-8-oxoguanosine (loxoribine). All of the compounds enhance natural killer (NK) activity, lymphocyte proliferation, and antibody production in dose-dependent fashion. However, the potency and maximal activity of the disubstituted analogues are considerably greater than those of the monosubstituted analogues. Spleen cells stimulated for 48 h with the disubstituted compounds produce immunoreactive interleukin (IL) 1 alpha, IL-6, tumor necrosis factor-alpha (TNF alpha), and interferon-gamma (IFN gamma). Monosubstituted analogues induce lower quantities of IL-6, TNF alpha, and IFN gamma and fail to induce detectable levels of IL-1 alpha. Total IFN activity, assessed by viral inhibition assay, is also lower for the monosubstituted analogues. Augmentation of antibody secretion by B cells is diminished for neither mono- nor disubstituted compounds upon incubation with anti-cytokine antibodies. In contrast, anti-IFN alpha beta markedly reduces the effects of monosubstituted analogues on NK activity but has less marked effects on NK induction by the disubstituted compounds. A similar pattern of differences is seen for lymphocyte proliferation. Thus, although the analogues induce synthesis of several cytokines, to date only IFN alpha beta appears directly involved in enhancement of NK activity and lymphocyte proliferation. The present data do not, however, exclude the existence of an autocrine stimulatory mechanism not susceptible to inhibition by anti-cytokine antibodies.
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PMID:Enhancement of immunostimulatory activity by dual substitution of C8-substituted guanine ribonucleosides: correlation with increased cytokine secretion. 764 61

We previously reported that the extract of seeds from Aeginetia Indica L (AIL), a parasitic plant, induces potent antitumor immunity in tumor-bearing mice and that CD4+ T cells appear to be the main contributors in the induction of antitumor resistance. The present study was set up to investigate the in vitro effects of AIL on various lymphoid cells. Spleen cells from mice pretreated with AIL every 2 days for 1 week produced interleukin 2 (IL-2), interferon gamma (IFN gamma), tumor necrosis factor (TNF) and interleukin 6 (IL-6) when these cells were stimulated in vitro by AIL. Further, we found that CD4+ T cells were main producers of IL-2 and TNF upon the stimulation with ALL in vitro, while both CD4+ and CD8+ T cells secreted IFN. On the other hand, ALL was mitogenic in vitro to T enriched splenic lymphocytes as well as B enriched splenic lymphocytes. Moreover, AIL also proliferated thymocytes and this activity was potently synergistic with a suboptimal dose of concanavalin A (Con A). Lipopolysaccharide (LPS) contamination in AIL preparation was negligible since proliferative activity of AIL to B enriched splenic lymphocytes was not influenced in the presence of an endotoxin antagonist, polymyxin B sulfate (PMB). Further, B cell mitogenic activity of AIL seems to be mediated by different mechanism(s) from that of LPS since ALL could proliferate B enriched lymphocytes of C3H/HeJ mice which do not respond to the stimulation with LPS. A well known biological response modifier (BRM), Krestin (PSK), had no ability in inducing either T or B lymphocyte activation in vitro as shown by AIL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Seed extract of Aeginetia indica L induces cytokine production and lymphocyte proliferation in vitro. 820 51

Spleen cells from mice bearing progressively growing syngeneic sarcomas are immunologically hyporeactive and respond by significantly decreased proliferative response to stimulation with mitogens and cytokines. Here we show that these hyporeactive cells synthesize, after mitogen stimulation, comparable amount of mRNA for tumor necrosis factor (TNF)-alpha as do cells from control mice. However, stimulated spleen cells from the same tumor-bearing mice produce considerably less mRNA for TNF-beta than cells from control mice. These observations were further confirmed using purified peritoneal macrophages and enriched splenic T cells. The results thus demonstrate a distinct regulation of expression of genes for TNF-alpha and TNF-beta, two functionally very similar cytokines, and simultaneously a selective impairment of T-cell function in the course of growth of syngeneic tumors in mice.
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PMID:Expression of the gene for tumor necrosis factor-beta but not for tumor necrosis factor-alpha is impaired in tumor-bearing mice. 824 63

Experiments using a murine model of heat-killed Staphylococcus aureus-induced gram-positive bacterial sepsis indicate that the lethal bacterial effects can be prevented if mice are pretreated with CL 184,005, a platelet-activating factor (PAF) antagonist. CL 184,005 was ineffective when administered after bacterial challenge. Plasma of mice pretreated with CL 184,005 contained significantly less tumor necrosis factor (TNF), suggesting that CL 184,005 interferes with TNF synthesis induced by S. aureus. Spleen-associated TNF protein was also decreased by pretreatment with CL 184,005. Although TNF levels were significantly decreased in mice treated with CL 184,005, interleukin-6 levels in serum were significantly increased. Athymic mice were also susceptible to the lethal effects of S. aureus, suggesting that T cells were not involved. When rats rendered hypotensive with S. aureus were treated with CL 184,005, their blood pressure was normalized. Mice treated with enterotoxin B were not protected if they were pretreated with CL 184,005; however, TNF levels in these mice were significantly lower, suggesting that mediators other than PAF and TNF may contribute to the lethal effects of enterotoxin.
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PMID:Effect of CL 184,005, a platelet-activating factor antagonist in a murine model of Staphylococcus aureus-induced gram-positive sepsis. 827 76

Chronic ethanol (ETOH) ingestion adversely affects the immunocompetence of alcohol abusers. ETOH directly impairs host defense mechanisms and indirectly modulates immunocompetence by interfering with the nutritional status of the alcoholic. It is not clear from the current literature, however, to what extent ETOH, nutritional status, or the combination of the two factors modulates immune mechanisms in chronic alcoholics. To date, most animal studies investigating the immunotoxicity of ETOH have neglected the dietary factors, which may have masked additional immunotoxic effects of ETOH. To examine these dietary factors, we fed mice three liquid ETOH diets with different dietary sufficiencies for 7 weeks and investigated various immune responses. Spleen cell number and secretions of immunoreactive interleukin-2 and tumor necrosis factor were totally independent of the diet, being affected only by ETOH. Body, spleen, and thymus weights, interferon-gamma secretion, and natural killer cell and phagocytic activities were modulated by ETOH as well as by diet. Natural killer cell and phagocytic activities were also directly affected by the nutritional quality of the diet. These results suggest that animal diets used in experimental studies of ETOH-induced immunomodulation must be planned and controlled carefully in order to single out the direct effects that ETOH has on the host defense system.
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PMID:Diet and ethanol modulate immune responses in young C57BL/6 mice. 833 93


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