Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin (IL)-4 has been implicated in the pathogenesis of leishmaniasis in a murine model. Experiments were done to examine the effect of IL-4 on cytokine activation of macrophages. Interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha), and IL-3 activate macrophages to inhibit replication of leishmaniae. IL-4 abrogated in a dose- and time-dependent manner the induction of antileishmanial activity by these cytokines. The depression of oxidative burst capacity is one mechanism by which IL-4 inhibits macrophage activation. IL-4 diminished in a dose- and time-dependent manner the TNF alpha enhancement of oxidative capacity. Pretreatment with IL-4 for 48, 24, or 0 h, respectively, inhibited the generation of superoxide induced by TNF alpha by 90%, 60%, and 40%. Furthermore, IL-4 abrogated the enhancement of oxidative capacity by IFN-gamma, GM-CSF, and IL-3. These data suggest that IL-4 is a potent deactivator of macrophage antimicrobial functions and may contribute to the pathogenesis of visceral leishmaniasis.
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PMID:Interleukin-4 inhibits human macrophage activation by tumor necrosis factor, granulocyte-monocyte colony-stimulating factor, and interleukin-3 for antileishmanial activity and oxidative burst capacity. 130 48

The influence of cytokines on extracellular superoxide dismutase (EC-SOD) expression by human dermal fibroblasts was investigated. The expression was markedly stimulated by interferon-gamma (IFN-gamma), was varying between fibroblast lines stimulated or depressed by interleukin-1 alpha (IL-1 alpha), was intermediately depressed by tumor necrosis factor-alpha (TNF-alpha), and markedly depressed by transforming growth factor-beta (TGF-beta). TNF-alpha, however, enhanced the stimulation by a high dose of IFN-gamma, whereas TGF-beta markedly depressed the stimulations given by IFN-gamma and IL-1 alpha. The ratio between the maximal stimulation and depression observed was around 30-fold. The responses were generally slow and developed over periods of several days. There were no effects of IFN-alpha, IL-2, IL-3, IL-4, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, human growth hormone, Escherichia coli lipopolysaccharide, leukotriene B4, prostaglandin E2, formylmethionylleucylphenylalanine, platelet-activating factor, and indomethacin. The cytokines influencing the EC-SOD expression are also known to influence superoxide production by leukocytes and other cell types, and the EC-SOD response pattern is roughly compatible with the notion that its function is to protect cells against extracellular superoxide radicals. The results show that EC-SOD is a participant in the complex inflammatory response orchestrated by cytokines. The CuZn-SOD activity of the fibroblasts was not influenced by any of the cytokines, whereas the Mn-SOD activity was depressed by TGF-beta. TNF-alpha, IL-1 alpha, and IFN-gamma stimulated the Mn-SOD activity, as previously known, and these responses were reduced by TGF-beta. The different responses of the three SOD isoenzymes illustrate their different physiological roles.
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PMID:Regulation by cytokines of extracellular superoxide dismutase and other superoxide dismutase isoenzymes in fibroblasts. 155 78

Benzene is a widely used industrial solvent known to cause bone marrow depression. This is associated with increased production of reactive oxygen metabolites and nitric oxide by bone marrow phagocytes, which have been implicated in hematotoxicity. Benzene metabolism to phenolic intermediates appears to be an important factor in bone marrow toxicity. In the present studies, we compared the effects of benzene and several of its metabolites on nitric oxide production by murine bone marrow leukocytes. Bone marrow cells readily produced nitric oxide in response to the inflammatory mediators lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Treatment of mice with benzene (800 mg/kg), or its metabolites hydroquinone (100 mg/kg), 1,2,4-benzenetriol (25 mg/kg), or p-benzoquinone (2 mg/kg), at doses that impair hematopoiesis, sensitized bone marrow leukocytes to produce increased amounts of nitric oxide in response to LPS and IFN-gamma. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) augmented bone marrow leukocyte production of nitric oxide induced by inflammatory mediators. Benzene, as well as its metabolites, markedly increased the sensitivity of the cells to both GM-CSF and M-CSF. Cells from hydroquinone- or 1,2,4-benzenetriol-treated mice were significantly more responsive to the inflammatory cytokines and growth factors than cells isolated from benzene- or p-benzoquinone-treated mice, suggesting that the phenolic metabolites of benzene are important biological reactive intermediates. Because nitric oxide suppresses cell growth and can be metabolized to mutagens and carcinogens, the ability of benzene and its metabolites to modulates its production in the bone marrow may be important in their mechanism of action.
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PMID:Distinct actions of benzene and its metabolites on nitric oxide production by bone marrow leukocytes. 788 13

Polymorphonuclear leukocytes (PMNLs) exposed to influenza A virus (IAV) undergo activation of the respiratory burst followed by depression of cell function when subsequently exposed to particulate or soluble stimuli. The effect of IAV on PMNLs is likely to be mediated through the attachment of IAV to one or more specific receptors. Recently, IAV has been shown to bind to the sialophorin protein (CD43) receptor on PMNL plasma membranes. The present study was performed to determine if the sialophorin receptor was responsible for IAV-induced PMNL dysfunction. When PMNLs were incubated with IAV or CD43 monoclonal antibody (MoAb) for 30 minutes and then exposed to a secondary particulate (opsonized zymosan) or soluble (FMLP or phorbol 12-myristate 13-acetate) stimulus, there was significant depression of the PMNL chemiluminescence response compared with the equivalent control (P < .05). When PMNL were incubated with the CD43 MoAb and then cross-linked with a goat antimouse IgG antibody, no depression of PMNL function occurred upon secondary stimulation. Exposure of cells to IAV aggregates also eliminated the PMNL dysfunction that normally occurs due to the virus. Similar to IAV, PMNL dysfunction due to the CD43 MoAb could be overcome by priming the cells with granulocyte-macrophage colony-stimulating factor. These findings indicate that IAV-induced PMNL dysfunction is mediated, at least in part, through the sialophorin receptor.
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PMID:Role of the sialophorin (CD43) receptor in mediating influenza A virus-induced polymorphonuclear leukocyte dysfunction. 788 80

Nitric oxide is a short-lived reactive mediator that inhibits bone marrow (BM) cell proliferation induced by granulocyte-macrophage colony-stimulating factor (GM-CSF). The present studies show that nitric oxide also inhibits macrophage colony-stimulating factor (M-CSF)-induced growth of mouse BM cells, an effect that was dependent on the presence of an inflammatory mediator and blocked by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMA). Treatment of mice with the hematotoxicant benzene (800 mg/kg, intraperitoneally, two times per day, for 2 days) resulted in a significant increase in nitric oxide production by BM cells stimulated with lipopolysaccharide (LPS) and interferon gamma alone or in combination with M-CSF or GM-CSF. Cells from benzene-treated mice also displayed increased sensitivity to the growth-promoting effects of M-CSF and GM-CSF. These results suggest that benzene treatment of mice primes BM cells to inducers of nitric oxide. Northern blot analysis showed that this was, at least in part, caused by increased expression of mRNA for inducible nitric oxide synthase (iNOS). Surprisingly, treatment of mice with L-NMA was found to cause a depression in BM cell proliferation and to potentiate benzene-induced decreases in BM cellularity and increases in nitric oxide production. L-NMA administration also augmented nitric oxide production by BM cells. These data indicate that L-NMA is hematotoxic and suggest that it may have actions distinct from inhibition of nitric oxide synthase in the BM.
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PMID:Enhanced production of nitric oxide by bone marrow cells and increased sensitivity to macrophage colony-stimulating factor (CSF) and granulocyte-macrophage CSF after benzene treatment of mice. 819 60

An unusual instance of severe and potentially lethal depression of the bone marrow is described as a result of the administration of phenytoin for seizure prophylaxis. The patient was treated successfully by prompt cessation of phenytoin and intravenous administration of human recombinant granulocyte-macrophage colony-stimulating factor.
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PMID:Severe phenytoin-induced bone marrow depression and agranulocytosis treated with human recombinant granulocyte-macrophage colony-stimulating factor. Case report. 831 50

The activity of four recombinant human cytokines on porcine neutrophils was evaluated. Porcine neutrophils were treated with varying doses of recombinant human tumour necrosis factor-alpha (rHu-TNF), interferon-gamma (rHu-IFN), interleukin-8 (rHu-lL-8), or granulocyte-macrophage colony-stimulating factor (rHu-GM-CSF). The function of treated neutrophils was compared with that of non-treated controls in the following assays: antibody-independent neutrophil cytotoxicity (AINC), antibody-dependent cell-mediated cytotoxicity (ADCC), iodination, Staphylococcus aureus ingestion, cytochrome C reduction, random migration, and chemotaxis. Treatment with rHu-TNF produced significant (P < 0.05) depression of neutrophil random migration (2.5, 25, and 250 ng ml-1 rHu-TNF) and iodination (250 ng ml-1) and a near significant (P = 0.08) depression in ADCC (250 ng ml-1). Treatment with 25,000 U ml-1 of rHu-IFN caused a significant increase in AINC. At lower doses of rHu-IFN, there was a trend (0.05 < P < or = 0.08) toward depression of AINC (250 U ml-1) and ADCC (25 U ml-1) and enhancement of iodination (250 U ml-1). Treatment with 50 ng ml-1 of rHu-IL-8 caused a near significant increase (P = 0.06) in AINC. There were no significant differences noted when porcine neutrophils were treated with rHu-GM-CSF (2.5-2500 U ml-1). No synergism was noted between rHu-TNF and rHu-IFN.
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PMID:Effect of recombinant human cytokines on porcine neutrophil function. 839 2

In the sequelae of massive traumatic stress, substantial impairment of immunologic reactivity has been demonstrated to correlate clinically with increased susceptibility to serious infection. Posttraumatic immune abnormalities consist basically of two coexistent mechanisms: Hyperinflammation and depression of cell-mediated immune responses. It is our understanding that the endogenous ability of the organism to survive overwhelming trauma is insufficient and requires exogenous support to prevent the conversion from systemic inflammatory response syndrome to bacterial sepsis and septic shock. The objectives of immunomodulatory interventions, which should be started as early as possible after tissue destruction, include a) prevention of excessive macrophage stimulation via neutralization of circulating endotoxins and exotoxins with high doses of polyvalent immunoglobulin and soluble complement receptors, b) global short-term (<72 hrs) down-regulation of inflammatory monocyte/macrophage and polymorphonuclear neutrophil activity, and c) restoration of cell-mediated immune performance to overcome posttraumatic functional paralysis. Among recent promising strategies, the use of granulocyte-macrophage colony-stimulating factor, pentoxifylline, and recombinant human interleukin-13 has been suggested, all of them predominantly down-regulating the Mphi (monocyte/macrophage) inflammatory potential. Cyclooxygenase inhibitors such as indomethacin and thymomimetic peptides can help normalize the immunoreactivity by restoring the forward-regulatory pathway of cell-mediated immunity responses. The efficacy of interferon to reduce infection and deaths in severely injured patients has been assessed in clinical trials. Still other compounds, i.e., CNI-1493, interleukin-11, tissue factor pathway inhibitors, and PGG-Glucan represent auspicious immunomodulatory approaches for control of posttraumatic or postoperative infections.
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PMID:Therapeutic immunomodulatory approaches for the control of systemic inflammatory response syndrome and the prevention of sepsis. 965 18

Dysregulation of both B- and T-cell responses is observed in leprosy. Immunoglobulin G1 (IgG1) and IgG3 antibody subclasses are selectively elevated towards the lepromatous or disseminated form of the disease accompanied by a depression of T-cell responses. T-cell and macrophage cytokines influence antibody class switching, differentiation and proliferation of B cells. To understand the dynamic nature of the immune response in leprosy, we examined the relationship between circulating Mycobacterium leprae-specific antibodies and secreted cytokines [interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-5, IL-10, IL-6, tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF)] in leprosy patients (19 lepromatous patients; 25 tuberculoid patients) and their exposed household contacts (HC=14) in response to M. leprae antigens. Paired comparison revealed a highly significant negative correlation between IFN-gamma and IgG (P=0.016), IgG1 (P<0.001) and IgG3 (P=0. 007) antibodies. No significant relationship was observed with other T-cell cytokines (IL-2, IL-5 and IL-10). These results strongly suggest that IFN-gamma may play a role in down-regulating antigen-specific IgG1 and IgG3 antibodies. Among the macrophage cytokines, TNF-alpha and GM-CSF which have not been shown to play a role in B-cell activation were positively associated with IgG1 (TNF-alpha, P=0.0005; GM-CSF, P=0.001) and IgG3 (TNF-alpha, P=0.001; GM-CSF, P=0.021) antibodies. Since macrophages have high-affinity Fc receptors for IgG1 and IgG3, it is possible that antigen uptake via these receptors may influence cytokine expression of TNF-alpha, a key modulator of disease pathogenesis in mycobacterial diseases. We are currently investigating the role of Fc receptors on activated macrophages, in expression of pro-inflammatory cytokines in mycobacterial diseases.
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PMID:Selective correlation of interferon-gamma, tumour necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor with immunoglobulin G1 and immunoglobulin G3 subclass antibody in leprosy. 1054 Feb 22

Apoptotic death of CD8(+) T cells can be induced by a population of inhibitory myeloid cells that are double positive for the CD11b and Gr-1 markers. These cells are responsible for the immunosuppression observed in pathologies as dissimilar as tumor growth and overwhelming infections, or after immunization with viruses. The appearance of a CD11b(+)/Gr-1(+) population of inhibitory macrophages (iMacs) could be attributed to high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in vivo. Deletion of iMacs in vitro or in vivo reversed the depression of CD8(+) T-cell function. We isolated iMacs from the spleens of immunocompromised mice and found that these cells were positive for CD31, ER-MP20 (Ly-6C), and ER-MP58, markers characteristic of granulocyte/monocyte precursors. Importantly, although iMacs retained their inhibitory properties when cultured in vitro in standard medium, suppressive functions could be modulated by cytokine exposure. Whereas culture with the cytokine interleukin 4 (IL-4) increased iMac inhibitory activity, these cells could be differentiated into a nonadherent population of fully mature and highly activated dendritic cells when cultured in the presence of IL-4 and GM-CSF. A common CD31(+)/CD11b(+)/Gr-1(+) progenitor can thus give rise to cells capable of either activating or inhibiting the function of CD8(+) T lymphocytes, depending on the cytokine milieu that prevails during antigen-presenting cell maturation. (Blood. 2000;96:3838-3846)
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PMID:Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. 1109 68


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