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)

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

The depression of vasoconstrictor responsiveness caused by bacterial lipopolysaccharide (LPS) is mediated, in part, by the induction of nitric oxide synthase (NOS) and the resultant increase in nitric oxide production by vascular smooth muscle. The present study evaluated the ability of the antioxidant, diethyldithiocarbamate (DDTC), to attenuate the LPS-stimulated induction of NOS in cultured vascular smooth muscle cells (VSMC) and the depression of in vitro vascular reactivity caused by LPS administration to rats. The LPS-stimulated increase in nitrite production by cultured VSMC was inhibited 85% by DDTC (100 microM). When VSMC were stimulated with a combination of LPS, interferon-gamma (INF) and tumor necrosis factor (TNF) nitrite production was 5-fold greater than with LPS alone. DDTC inhibited 49% of the increase caused by LPS plus INF and TNF. Aortic rings taken from animals injected with LPS showed a depression of maximum force in response to phenylephrine which was reversed by inhibition of NOS activity. Pretreatment of animals with DDTC attenuated this depression of vascular reactivity. The DDTC treatment did not reduce the increase in serum TNF levels caused by LPS. These results suggest that DDTC can attenuate the LPS-stimulated induction of NOS in vascular smooth muscle and may thereby ameliorate the impairment of vascular reactivity.
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PMID:Diethyldithiocarbamate ameliorates the effect of lipopolysaccharide on both increased nitrite production by vascular smooth muscle cells and decreased contractile response of aortic rings. 754 1

The aim of the present study was to determine whether two classical macrophage activators, bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) could affect the accumulation of the second messenger cAMP in cultured rat microglia and astrocytes. Purified microglia and astrocyte secondary cultures obtained from the neonatal rat were grown for 3 days in basal medium Eagle (BME) + 10% fetal calf serum (FCS). Exposure of microglia to LPS resulted into a dose- and time-dependent decrease in the accumulation of cAMP induced by receptor-mediated (isoproterenol or prostaglandin E2) or direct (forskolin) activation of adenylate cyclase. The inhibitory effect of LPS was rapid (a 10 min preincubation was sufficient to approach a maximal effect), occurred at low doses (IC50 = 1.2 ng/ml), and was not abrogated by pertussis toxin. A selective inhibitor of type IV phosphodiesterase (rolipram, 100 nM) prevented the effect of LPS on cAMP accumulation, while inhibitors of other forms of phosphodiesterase were unable to do so. IFN-gamma (100 u/ml) also caused a depression of the evoked cAMP accumulation in microglia after a 10 min preincubation, and its effect was prevented by rolipram, as in the case of LPS. Astrocytes differed from microglia in that LPS (1-100 ng/ml) did not inhibit the accumulation of cAMP induced by either isoproterenol or forskolin; on the other hand, IFN-gamma did have an inhibitory effect (though less pronounced than in microglia) that could be prevented by rolipram.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon-gamma and lipopolysaccharide reduce cAMP responses in cultured glial cells: reversal by a type IV phosphodiesterase inhibitor. 755 45

In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) the cytokines tumour necrosis factor-alpha (TNF), lymphotoxin-alpha (LT), and interferon-gamma (IFN-gamma) are of central pathogenetic importance. A therapy capable of stopping neurological deterioration in MS patients is not yet available. Here, we report that rolipram, a selective type IV phosphodiesterase inhibitor, stereospecifically suppresses the production of TNF/LT and less strongly also IFN-gamma in human and rat auto-reactive T cells. Moreover, we show that rolipram is an effective treatment for EAE. Rolipram has extensively been studied in humans for the treatment of depression, but has not yet been marketed. The data presented here identify rolipram as potential therapy for multiple sclerosis and provoke the immediate initiation of clinical trials.
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PMID:The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis. 758 35

In 54 patients with cHCV infection, peripheral immune responsiveness and soluble mediator release were evaluated. Results demonstrate that in these patients phagocytosis and killing capacities exerted by polymorphonuclear cells and monocytes were profoundly depressed. At the same time, absolute numbers of CD3+, CD8+ and CD16+ cells were reduced, while the CD4(+)-CD8+ dependent antibacterial activity was also impaired. With special reference to soluble mediators, elevated amounts of both soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1 were detected in sera of patients. By contrast, serum levels of tumor necrosis factor-alpha were within normal ranges, whereas interferon-gamma serum concentrations were decreased. Of note, in 18.5% of cHCV patients circulating levels of bacterial lipopolysaccharides (LPS) were detected by means of Limulus assay. In the Limulus+subset of patients, absolute numbers of CD14+ cells were reduced in a significant manner, this implying a putative monocyte-LPS interaction. In conclusion, the overall results indicate a condition of peripheral immune depression in cHCV patients with an exaggerated shedding of various mediators endowed with noxious effects for the host.
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PMID:Evaluation of cellular immune responses and soluble mediators in patients with chronic hepatitis C virus (cHCV) infection. 765 Feb 95

Hepatocellular carcinomas 1 cm in diameter with high or low echogenicity can be detected on ultrasonography and confirmed on fine-needle biopsy, but it is still very difficult to detect small hepatocellular carcinomas with isoechogenicity. In this study, we assessed lymphokine-activated killer cell activity and interferon-gamma production prospectively every 1 to 3 mo for 23 +/- 4 mo (mean +/- 1 S.D.) in 227 patients with cirrhosis. Transient depression of lymphokine-activated killer activity was detected in 43 patients (defective lymphokine-activated killer group), and hepatocellular carcinoma was detected in 24 cases before the end of the 18-mo follow-up. Twenty-one (87.5%) of the 24 hepatocellular carcinoma patients were included in the defective lymphokine-activated killer group. Defective lymphokine-activated killer activity was detected more than 6 mo before detection of a space occupying lesion in the liver or elevation of alpha-fetoprotein level above 400 ng/ml. Serum alpha-fetoprotein level was elevated above 400 ng/ml in only five cases in which hepatocellular carcinoma was detected as a space-occupying lesion. Our results indicate that sequential assessment of lymphokine-activated killer activity may be a predictor of hepatocellular carcinoma and that the depression of immune function in cirrhotic patients is a serious risk factor for hepatocellular carcinoma emergence.
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PMID:Depressed immune function in patients with cirrhosis before emergence of hepatocellular carcinoma. 768 81

Nocturnal (23.00-07.00 h) urinary melatonin and total biopterin (tBI; after acidic oxidation of reduced biopterins) were analyzed during the growth of two passages of a mammary tumor line in female F344 Fischer rats. In addition, nocturnal (02.00-03.00 h) peak concentrations of pineal melatonin in plasma were analyzed when tumors had reached comparable average tumor volumes of 25-30 cm3. Since tetrahydrobiopterin (BH4) is produced by murine macrophages in response to interferon-gamma released by activated T lymphocytes, measurements of tBI can serve to estimate the state of cellular immunity. At passage 2, a slow-growing localized carcinosarcoma, tBI showed a progressing increase during tumor growth reaching more than 200% (p < 0.05-0.005) of controls by the end of the experiment. Urinary and plasma melatonin were elevated by 30-50% (p < 0.05) and 42% respectively. At passage 12, a fast-growing metastasizing sarcoma, a depression of about 20-30% was found for tBI (p < 0.05) and urinary melatonin (p < 0.025); plasma melatonin was depleted by 70% (p < 0.005). Parallel changes of both parameters at each tumor passage indicate a close link between the pineal hormone melatonin and cellular immunity. The opposite trends observed at the two passages indicate a clear stimulation of the immune system and the pineal gland at early but inhibition at advanced stages of cancer.
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PMID:Serial transplants of DMBA-induced mammary tumors in Fischer rats as model system for human breast cancer. IV. Parallel changes of biopterin and melatonin indicate interactions between the pineal gland and cellular immunity in malignancy. 777 39

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

We have studied the relationship between the cytokine production induced in vivo by prolonged isometric exercise and the symptom complex marked by fatigue in patients with chronic fatigue syndrome (CFS). Twelve male patients and 13 matched male control subjects undertook an isometric hand-grip exercise protocol utilizing dynamometers. Subjects undertook 30 minutes of exercise, for which the target force was set at 40% of the maximal voluntary contraction and the duty cycle was 50%. Prior to, during, and for 24 hours following the exercise, blood samples were collected and assayed for the presence of cytokines, including interferon-gamma and interferon-alpha, interleukin-1 beta, and tumor necrosis factor-alpha. At those times subjects also completed the Profile of Mood States (POMS) questionnaire, which served as a measure of changes in subjective fatigue. No significant alteration in the level of any of the cytokines in the plasma of patients or control subjects was detected before, during, or after exercise. Surprisingly, the patients' levels of fatigue, depression, and confusion, as measured by the POMS, decreased in response to the exercise. These data do not confirm the presence of an immunologic process correlating with the exacerbation of fatigue after exercise experienced by patients with CFS. Limitations in the study design and in the sensitivity of the cytokine assays may have affected our results.
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PMID:Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise. 814 42

Cytokines are thought to cause the depression of cytochrome P-450 (CYP)-associated drug metabolism in humans during inflammation and infection. We have examined the role of five cytokines, i.e., interleukin-1 beta, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma, on the expression of CYP1A2, CYP2C, CYP2E1, CYP3A, and epoxide hydrolase in primary human hepatocyte cultures. Steady state P-450 and epoxide hydrolase mRNA levels, as well as ethoxyresorufin-O-deethylase and nifedipine oxidation activities, which are mainly supported by CYP1A1/1A2 and CYP3A, respectively, were measured. Interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha were found to be the most potent depressors of P-450 enzymes. After 3 days of treatment, both mRNA levels and enzyme activities were depressed, typically by at least 40%, whatever the cytokine and the enzyme considered. Interferon-gamma also suppressed CYP1A2 and CYP2E1 mRNA levels and ethoxyresorufin-O-deethylase activity but had no effect on CYP3A and epoxide hydrolase mRNAs. In addition, interleukin-4 had the opposite effect, compared with other cytokines, on CYP2E1 mRNA, which was increased up to 5-fold; ethoxyresorufin-O-deethylase and nifedipine oxidation activities were not significantly affected. These results provide the first demonstration that various cytokines act directly on human hepatocytes to affect expression of major P-450 genes and that a wide range of responses can be observed among the enzymes for a given cytokine, suggesting that different regulatory mechanisms may be involved.
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PMID:Cytokines down-regulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture. 823 20


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