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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of procoagulant activity by circulating monocytes and its regulation by a cytokine secreted by mitogen-stimulated peripheral blood mononuclear cells was investigated in recipients of HLA-identical sibling bone marrow transplants. Blood monocyte numbers reached the normal range within 3 weeks of transplant. After stimulation with lipopolysaccharide, macrophage procoagulant activity was found to be within the normal range in all patients at all times post transplant. It did not appear to correlate with the presence or absence of graft-versus-host disease. Surprisingly, and in marked contrast to our previously documented severe depression of interleukin 2 production by transplant recipients' peripheral blood mononuclear cells, the mitogen-induced production of the cytokine that induces procoagulant activity production (macrophage procoagulant inducing factor, MPIF) was also normal in the majority of patients when assayed using the responsive myelomonocytic cell line RC-2A. These findings suggest firstly that monocyte differentiation and function normalize rapidly post transplant; and secondly, when taken together with previous studies, that the ability of peripheral blood mononuclear cells to synthesize cytokines post transplant varies greatly according to the specific cytokine involved.
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PMID:Cytokine activity after human bone marrow transplantation. II. Production of macrophage procoagulant activity and the cytokine regulating its production, macrophage procoagulant inducing factor. 329 28

Sepsis due to impaired host defence mechanisms is one of the most frequent causes of death in severely burned patients. However, it is not precisely known to what extent syntheses and release of suppressive mediators of the burned tissue affect the cellular and humoral immune responses. In this study a decreased production of plasminogen activator by macrophages is demonstrated after incubation with skin components, indicating a decreased macrophage helper function for T-B cell cooperation. An additional effect of the skin fraction is a considerable increase in mitogenic activity as measured in the antibody-forming cell test. This enhancement of macrophage-T-B cell cooperation is concentration dependent and lower in the burned skin fraction as compared to the unburned control. A known skin-derived cytokine with mitogenic properties is epidermal cell-derived thymocyte activating factor (ETAF) exhibiting interleukin-1 (I1-1) like activity including mitogenic enhancement of murine thymocyte stimulation by phytohaemagglutinin. Burned and control skin fraction as tested in a thymocyte assay did not show interleukin-1-like activity. The experiments suggest the presence of a skin-derived growth factor which is not interleukin-1 but which stimulates T-B cell cooperation when there is depression of macrophage function. Further purification is required in order to assess the clinical relevance of the factor in burned patients.
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PMID:Changes in the cellular immune response by a subfraction of burned murine skin. 348

Administration of whole-cell diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) caused marked depression in the expression of mRNA for isozymes of cytochrome P-450 in the livers of endotoxin-responsive and nonresponsive mice. The levels of expression of mRNA for a polycyclic aromatic hydrocarbon-inducible (CYP1A2) and an ethanol-inducible (CYP2E1) form of P-450 were reduced by 70% to 80% 8 to 12 hr after vaccination or Bordetella pertussis endotoxin administration. These effects are preceded by marked increases (threefold to sixfold) in mRNA expression for interleukin-6, interleukin-1 and tumor necrosis factor in both strains of mice, with maximal increases 1 to 2 hr after injection. This is the first demonstration that levels of cytokine mRNA are altered in the liver in response to DTP vaccine administration. The finding of increased cytokine mRNA in the livers of mice injected with vaccine supports a role for cytokines as mediators of the decreased levels of cytochrome P-450. In addition, inducible nitric oxide synthase mRNA expression is also increased after vaccine administration, with a peak at 4 hr. The temporal relationship of the increased cytokine mRNA expression, increased nitric oxide synthase and decreased expression of P-450 mRNAs suggests a mechanism by which cytokines mediate the induction of nitric oxide synthase, which increases nitric oxide and decreases the activities of some cytochromes P-450.
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PMID:Modulation of hepatic mRNA levels after administration of lipopolysaccharide and diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) to mice. 752 68

We and others have proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. An effect of NO on cardiac sarcolemmal L-type calcium channels has also recently been proposed. The spontaneous beating rate of neonatal cardiac myocytes is regulated by the sarcolemmal L-type calcium channel. Accordingly, we sought to determine if cytokine-stimulated NO production could also regulate beating rates of neonatal cardiac myocytes. Treatment of neonatal rat cardiac myocytes with TNF, IL-1, IL-6, 10(-5)M NMA, or 10(-3)M NMA significantly enhanced spontaneous beating rates compared to untreated myocytes in serum-free media for 48 hours (p < or = .01; n = 12 for each). Only IL-1 treatment resulted in significant nitrite levels vs. control over 48 hours (4.2 +/- 0.7 vs. 0.3 +/- 0.2 nmoles/1.25 x 10(-5) cells, respectively) (n = 12). Nitrite production by IL-1 was inhibited by 10(-3)M NMA but not 10(-5)M NMA (0.3 +/- 0.2 vs. 4.1 +/- 0.6 nmoles; p < .01; n = 12). The addition of 10(-5)M NMA to TNF, IL-1, and IL-6 did not alter the effect of the cytokines on the spontaneous beating rates of the cardiac cells (p < or = .01; n = 12 for each). These results strongly suggest that cytokines and NMA affect cardiac myocyte spontaneous beating rates through mechanisms independent of NO.
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PMID:Chronotropic effects of cytokines and the nitric oxide synthase inhibitor, L-NMMA, on cardiac myocytes. 752 6

1. Myocardial dysfunction during septic shock is associated with enhanced production of cytokines such as interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha). These cytokines depress cardiac mechanical function by a mechanism which is not well defined. 2. Bacterial endotoxin or cytokines cause the expression of Ca(2+)-independent nitric oxide (NO) synthase in cardiac myocytes, vascular endothelial cells and endocardial endothelial cells, causing enhanced production of NO. As NO has negative inotropic actions on cardiac muscle, we tested the sum effects of IL-1 beta plus TNF-alpha in the intact heart to determine whether enhanced expression of NO synthase activity in the cells that comprise the heart is involved in cardiac depression associated with cytokine stimulation. 3. Rat isolated working hearts perfused with IL-1 beta plus TNF-alpha showed a markedly greater depression in contractile function, measured as cardiac work, after 2 h of perfusion compared with time-matched control hearts. The depressant action of IL-1 beta plus TNF-alpha was first apparent after 1 h of perfusion; no early (15 min) cardiac depressant actions were seen. 4. The competitive inhibitor of Ca(2+)-dependent and Ca(2+)-independent NO synthases, NG-nitro-L-arginine methyl ester (L-NAME, 3 microM) when given concurrently with IL-1 beta plus TNF-alpha prevented the loss in contractile function such that these hearts after 2 h of perfusion had similar function to time-matched controls. L-NAME did not acutely reverse the loss of contractile function in hearts exposed for 2 h to IL-1 beta plus TNF-alpha. The protective action of L-NAME in the presence of cytokines was concentration-dependent and was not seen at a higher concentration (10 micro M) due to the significant reduction in coronary flow observed at this concentration.5. In contrast, when L-NAME (3 micro M) was given in the absence of IL-l beta plus TNF-alpha it depressed contractile function over the 2 h perfusion period by significantly reducing coronary flow.6. Inhibition of protein synthesis with cycloheximide (Cx) abolished the loss in function that occurred over 2h in both control and IL-1 beta plus TNF-a-treated hearts.7. Inducible, Ca2+-independent NO synthase activity was not observed in freshly isolated hearts but was observed in control hearts perfused for 2 h in vitro and was doubled in hearts perfused with IL-1 beta plus TNF-a. Cx prevented the expression of Ca2+-independent NO synthase in both control and cytokine-treated hearts.8. In summary, these results suggest that the depression of myocardial function by IL-l beta plus TNF-alpha is mediated, at least in part, by induction of Ca2+-independent NO synthase activity in the heart.
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PMID:The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha. 753 96

One, as yet unemployed, approach to investigating immunology in depression is the assessment of the cytokine production by leucocytes, which would allow the determination of immune response under standardized conditions. Thus we measured the production of mitogen-induced cytokines (IL-1 beta, IL-2, IL-6, IL-10, interferon-gamma) and sIL-2R in a whole blood assay, and serum protein levels such as C-reactive protein (CRP), haptoglobin (Hp) and alpha 2-macroglobulin (alpha 2 M) in a longitudinal 6-week study in an attempt to assess leucocyte function during and after acute clinical stage of depression in 39 patients. Shortly after admission to hospital we found higher levels of all measured cytokines in the patients. Serum protein levels were significantly higher in the patients than in controls, and decreased over the study period. Whereas slightly elevated monokine levels in patients tended to reach control values, lymphokines showed a significant decrease over the 6 weeks as compared to baseline. These results suggest that the increase in immune activity seen at the beginning of the study may be followed by a suppressed cell-mediated immune function.
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PMID:Cytokine production and serum proteins in depression. 753 45

Short-chain fatty acids are a major by-product of anaerobic metabolism and can be detected in gingival fluid from periodontal pockets. Since most T cells are present subjacent to the pocket epithelium in conjunction with the plasma cells, it is important to know how these T cells are affected by short-chain fatty acids produced by subgingival plaque. The purpose of this study is to examine the effects of extracellular metabolites from periodontopathic bacteria on the proliferation and cytokine production of mouse splenic cells as a potential mechanism of imbalance among host-microbial interactions. A low-molecular-weight, heat-stable agent present in the two-day culture filtrate of Porphyromonas gingivalis, Prevotella loescheii, and Fusobacterium nucleatum significantly depressed Con A- and LPS- induced cell proliferation. To determine whether short-chain fatty acids present in the filtrate could account for the depression, we tested extracted volatile and non-volatile fatty acids for their effects on mitogenic activity. The volatile fatty acids extracted from immunosuppressive supernatants greatly inhibited T- and B- cell proliferation. Among these volatile fatty acids, butyric, propionic, valeric, and isovaleric acids impaired cell proliferation dose-dependently. From gas-liquid chromatographic analysis data, it is suggested that immuno-inhibitory activities in culture filtrates are mainly attributable to butyric and isovaleric acids in P. gingivalis, to propionic, butyric, and isovaleric acids in P. loescheii, and to butyric acid in F. nucleatum. Furthermore, these fatty acids significantly depressed interleukin 2 (IL-2), IL-4, IL-5, IL-6, and IL-10 production by Con A-stimulated splenic-T cells dose-dependently.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Volatile fatty acids, metabolic by-products of periodontopathic bacteria, inhibit lymphocyte proliferation and cytokine production. 756 Mar 87

We have previously proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. NO previously has been found to inhibit mitochondrial activity in other cell types. Accordingly, we sought to determine if cytokine-stimulated NO production inhibited cardiac myocyte mitochondrial activity. Treatment of neonatal rat cardiac myocytes with interleukin-beta (IL-1) resulted in the expression of mRNA for inducible NO synthase (iNOS) and stained positively for iNOS protein by immunohistochemistry. No iNOS staining was detected in untreated cells. IL-1 treatment resulted in significant nitrite levels vs control over 48 hrs (4.2 +/- 0.7 vs 0.3 +/- 0.2 nmol/1.25 x 10(5) cells, respectively) (n = 12) that was inhibited by 1mM NMA (0.3 +/- 0.2 nmoles; p < .01; n = 12). Mitochondrial activity was assessed by the MTT colorimetric assay using (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and OD 570-630. Mitochondrial activity was significantly inhibited by IL-1 vs control cells (0.436 +/- 0.01 vs 0.608 +/- 0.03) and reversed by 1mM NMA (0.549 +/- 0.03) or removal of IL-1 (0.662 +/- 0.02) (p < .01; n = 12 for each). These data strongly suggest that cytokine-stimulated NO production by cardiac myocytes results in reversible inhibition of mitochondrial activity.
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PMID:Cytokine-stimulated nitric oxide production inhibits mitochondrial activity in cardiac myocytes. 765 17

The pathology of aerosolized staphylococcal enterotoxin B (SEB) was studied in the nonhuman primate. Six juvenile rhesus monkeys that received multiple lethal inhaled doses of SEB developed diarrhea and vomiting within 24 hr followed by depression, dyspnea, and shock. Three of 6 animals died by 52 hr. The most striking gross lesion in all 6 monkeys was diffuse severe pulmonary edema. Histologically, edema fluid was present within the peribronchiolar, peribronchial, and perivascular interstitium, alveolar septa, and alveoli. The adventitia of pulmonary vessels was infiltrated by lymphocytes, macrophages, and fewer neutrophils. Numerous large lymphocytes with occasional mitotic figures were within pulmonary vessels, often occluding alveolar capillaries. These cells were strongly immunoreactive with monoclonal antibodies against CD3, establishing them as T cells. Ultrastructurally, endothelial cell junctions were intact, and endothelial cells and type I pneumocytes contained numerous pinocytotic vesicles. Alveolar septal interstitial spaces were expanded by edema. The mechanism of these SEB-induced pulmonary lesions was not determined. We hypothesize that cytokine production by activated T cells may have caused vascular permeability changes leading to widespread pulmonary edema and shock.
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PMID:Aerosolized staphylococcal enterotoxin B-induced pulmonary lesions in rhesus monkeys (Macaca mulatta). 765 51

The aetiology of the bone marrow suppression in HIV-infected patients is unknown. We have demonstrated previously that the ability of bone marrow cells, derived from mice made immunodeficient by infection with the retrovirus LP-BM5, to establish long-term stromal cultures is impaired. In this study we determined the ability of bone marrow stromal cells from these immunodeficient mice to produce cytokines important in haemopoiesis. Neither SCF, IL-3, GM-CSF nor TNF alpha were found in conditioned media of long-term bone marrow cultures (LTBMC) of normal or MAIDS mice. We failed to detect mRNA for TNF or IL-1 alpha, by reverse transcription polymerase chain reaction (RT-PCR), in cultures derived from either normal or immunodeficient mice. Steady-state levels of transcripts for IL-6 were equal in cells from normal and MAIDS mice. Steady-state levels of mRNA for TGF beta 1, a known inhibitor of haemopoiesis, were decreased in cultures derived from MAIDS mice at late stages of infection. The mRNA level of the multipotent haemopoietic regulator stem cell factor was also decreased in MAIDS cultures as compared with normals. Transcripts encoding the transmembrane form of the growth factor were almost absent. Addition of soluble GM-CSF and SCF only transiently increased the production of CFUs (BFUE and CFU-G/M) in MAIDS LTBMC. These findings suggest that derangements in cytokine production in stromal cells of immunodeficient mice may contribute to the suppression of haemopoiesis observed in this disease. One mechanism of HIV-induced depression of haemopoiesis may be via alterations of the haemopoietic microenvironment.
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PMID:Impaired cytokine production by bone marrow stromal cells of immunodeficient mice. 766 53


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