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)

The antiviral activity and induction of interferon-like substance by mepacrine (quinacrine, Atabrine) and Acranil in mice, described previuosly, was studied in more detail and compared with tilorone. The serum substance induced by Acranil was characterized as mouse interferon. Acranil, given parenterally, proved to be as strong as tilorone regarding interferon stimulation, in spite of the presence of only one side chain in the Acrainl molecule. Mepacrine was found to be a wealer interferon inducer than either tilorone or Acranil. The mode of interferon induction by Acranil and tilorone (effect of metabolic inhibitors, hyporesponsiveness to repeated doses, correlation between acute toxicity and antiviral activity, failure of effectiveness in chicks and chicken embryo tissue culture) was found comparable. However, the body temperature reactions of mice to the drugs were different: a striking hypothermic effect of tilorone, a lower one of mepacrine and the absence of body temperature depression by Acranil was observed.
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PMID:Comparison of the ability of small molecular interferon inducers: tilorone and acridine drugs. 120 Aug 45

Previous studies have shown that interferon (IF) preparations enhance phagocytic activity in cultured mouse peritoneal macrophages. It is shown here that cell culture fluids containing large amounts of IF, which had been treated with acid and clarified of the inducer, Newcastle disease virus, enhanced phagocytic activity when injected into mice. Enhanced phagocytic activity also was observed after injection of Newcastle disease virus into mice, but the contribution of IF to this event was unclear. The kinetics of the phagocytic response to inducers in vivo were biphasic. Depression of phagocytosis occurred around 16 to 18 h after injection of Newcastle disease virus. The observed enhancement began about 12 h later and lasted for at least 60 h more. It was concluded that the complexity of the response of mice to an inducer makes analysis of the role of IF in the ensuing events difficult. However, because of documented phagocytosis-enhancing effects of IF in vitro, it is very likely that the in vivo effects observed here are to some degree mediated by IF. On this basis, the concept of the activity of IF as a lymphokine is potentially expanded.
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PMID:Interferon preparations enhance phagocytosis in vivo. 127 6

The influence of spontaneous ketosis on interferon alpha and gamma production in blood leucocytes and on PHA induced lymphocyte blastogenic response was investigated. Twenty three cows 4.13 +/- 2.8 weeks after calving were divided into three experimental groups on the basis of blood ketone bodies, glucose and free fatty acids concentrations. The leukocytes of cows with clinical symptoms and the highest concentration of ketones and free fatty acids in blood responded with the lowest levels of interferons alpha and gamma to three interferon inducers: Newcastle Disease Virus (NDV), phytohemagglutinin (PHA) and concanavalin A (ConA). Depression in interferon PHA stimulated synthesis correlated with a very low mitogenic response of blood lymphocytes. Blood leukocytes of cows with subclinical ketosis, characterized by mild clinical symptoms and a lower concentration of ketones in blood in comparison to cows with clinical ketosis, responded better to interferon and mitogenic stimulation; however, the interferon titer and blastogenesis were still lower than in leukocytes of healthy cows. Correlation between the stage of ketosis and the level of interferon production in milk leukocytes was also observed. A possible relationship between the suppression of interferon production in blood leukocytes and the increased concentration of ketone bodies in blood is discussed.
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PMID:Suppression of interferon response of bovine leukocytes during clinical and subclinical ketosis in lactating cows. 128 Oct 68

Interferon and interferon inducers are well known to depress the cytochrome P450-dependent hepatic mixed-function oxidase system and cause a decrease in the capacity of the liver to metabolize drugs and xenobiotics. In this study we have shown that the interferon-mediated changes in an induced form of hepatic cytochrome P450 (CYP4A) are mediated via a depression in the levels of mRNA as assessed by Northern blot and slot blot analyses using a 20-base synthetic oligodeoxyribonucleotide hybridization probe. Rats were pretreated with clofibrate to maximize CYP4A mRNA levels prior to the administration of polyinosinic acid.polycytidylic acid (poly IC), an alpha/beta interferon inducer. Hepatic CYP4A mRNA levels were decreased by 49 and 30% at 6 and 24 hr, respectively, following poly IC administration. In hepatic microsomes cytochrome P450 and functional CYP4A as measured by lauric acid hydroxylation, were not affected at 6 hr, but were depressed by 39 and 27%, respectively, 24 hr following poly IC administration. These results suggest that interferon depresses induced levels of hepatic drug metabolism by lowering the level of cytochrome P450 mRNAs and subsequent synthesis of cytochrome P450 apoproteins.
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PMID:The suppression of hepatic cytochrome P4504A mRNA mediated by the interferon inducer polyinosinic acid.polycytidylic acid. 138 Aug 10

Since the discovery that interferon inducers depress hepatic drug metabolism, the depressant action of cytochrome P450 (P450) has been demonstrated to be shared by cytokines such as interferon alpha/beta and interferon gamma as well as interleukin-1 and tumor necrosis factor. Because these cytokines are inflammatory mediators, it is not surprising that theophylline toxicity has been reported in patients with influenza B epidemic. Hence, to lay a foundation for studies of altered steroid and drug metabolism, the alteration of P450 isozymes was studied after polyriboinosinic acid:polyribocitidylic acid (poly I:poly C) administration. Twenty-four hours after poly I:poly C administration, hepatic P450 content decreased to 57% of control, whereas depression of other microsomal enzymes was less pronounced: P450 reductase (69%), cytochrome b5 (74%) and NADH-cytochrome b5 reductase (85%). The depression of mRNA for cytochrome P450 1A1, 1A2, 2C11 and 2E1 was more than 60% of the controls. Recovery of mRNA levels was not complete within 72 hr. The changes in mRNAs, in general, paralleled alterations of monooxygenase activities and P450 isozyme content suggesting that the effect of poly I:poly C is pretranslational for all P450 isozymes studied. No overt differential effect on P450 isozymes was found after an administration of poly I:poly C. This study complements the previous report which demonstrated down-regulation of mRNA for cytochrome P450 2C11 and 3A2.
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PMID:Suppression of hepatic drug metabolism by the interferon inducer, polyriboinosinic acid:polyribocitidylic acid. 140

Various effects of glucocorticosteroids on the avian immune system were examined in chickens treated intramuscularly with 0.1 to 2.5 mg dexamethasone or prednisolone. Kinetic changes in body weight gain, percentages of lymphocyte subpopulations, and T-cell functions were examined following treatment with dexamethasone or prednisolone every other day. Chickens treated with dexamethasone or prednisolone showed a decrease in body-weight gain compared with age-matched, untreated chickens. In general, the total number of splenic lymphocytes of chickens treated with the two drugs was significantly lower than in controls in a dose-dependent manner. Flow cytometric analysis of splenic lymphocyte subpopulations revealed that the percentages of lymphocytes expressing CD8, gamma delta T-cell receptor, Ia, or IgM antigens and natural killer cells were lower in dexamethasone-treated chickens than in the controls, whereas the percentages of T lymphocytes bearing CD3, CD4, or alpha beta TCR antigens were higher. Furthermore, splenic T cells obtained from dexamethasone-treated chickens showed a significant depression in concanavalin A-induced lymphoproliferation and interleukin 2 and gamma-interferon production. The results characterize a variety of immunosuppressive effects of glucocorticoids on the avian immune system.
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PMID:Effects of corticosteroids on lymphocyte subpopulations and lymphokine secretion in chickens. 141 90

A total of 12 patients with advanced renal cell carcinoma received interferon alpha (3 million units intramuscularly 6 times weekly) and OK-432 (5 KE (Klinische Einheit) intramuscularly twice weekly). Metastatic lesions appeared before operation in six patients and after operation in six patients. Among them 5 patients had received interferon therapy and this combination therapy was started after the judgment of progressive disease for interferon therapy. Eleven pulmonary and 5 bone metastases were evaluable. The median duration of the combination therapy was 89.3 weeks. There were 4 partial responses and no complete responses among the 12 patients, giving a response rate of 33.3%. The median duration of response was 25 months, with a range of 6 to 54 months. Responses were seen predominantly in patients in whom metastases appeared after operation (3 of 4 responders). However, regarding the individual organs, two complete and 2 partial responses were observed among 11 pulmonary metastases and 2 partial responses among 5 bone metastases. The survival period after discovery of the metastasis was 10 to 67 months and the 5-year survival rate was 70.5%. Almost all patients had fever and induration at the injection site. Other side effects included leukopenia, anorexia, and depression. This combination therapy is thought to be effective against bone or other organs metastasis resistant to interferon alone.
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PMID:[Treatment of advanced renal cell carcinoma with interferon alpha and OK-432 (streptococcal preparation)]. 148 85

During episodes of infectious disease the mixed function oxidase system is depressed and the capacity of the liver to metabolize drugs can be compromised in both animals and humans. The depression that occurs during viral infections is mediated via the production of interferon. This action of interferon requires the synthesis of an intermediate protein(s) yet to be identified. Using an oligonucleotide probe for a unique sequence in cytochrome P-450LA omega we have now shown that the mRNA for this isozyme is depressed following the administration of interferon inducers. The magnitude in the loss of mRNA corresponds to the magnitude of the loss in the levels of this isozyme. This depression is observed within 6 h of interferon exposure. It is concluded that the decrease in drug metabolism during viral infections is caused by an interferon-mediated loss in mRNA and subsequent cytochrome P-450 synthesis in the liver.
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PMID:Regulation of hepatic cytochrome P-450 during infectious disease. 169 39

Modulation of the immune response by the use of biological response modifiers (BRM) is aimed at amplifying the host resistance against cancer. Studies on inhibition of tumor growth on an in vitro model, in which human breast carcinoma (HBL-100) and human lung carcinoma (H125) cells were used as target tumor cells, confirmed that interferons (IFNs) alpha and beta can amplify the antineoplastic effects of immunochemotherapy by enhancing the cytotoxic activity of effector cells and by antagonizing the immunodepressive effects of radiation or anticancer drugs. Moreover, data obtained from a pilot clinical trial, designed to test the effect of low concentrations of beta-IFN on natural cell-mediated cytotoxicity, pointed out a good correlation between the in vitro and in vivo responsiveness to beta-IFN in cancer patients. The immunomodulating and antiproliferative effects of BRM were also evaluated in a model of viral leukemogenesis in vitro, after infection of cord blood derived mononuclear cells (CB-MNC) with the human leukemic retrovirus HTLV-I. Alpha-and beta-IFN were previously shown to regulate differentially the antiviral competence of recipient CB-MNC, by interfering with viral replication and delaying the emergence of the transformed clone(s). One of the mechanisms of IFN action that contributes to control HTLV-I infection in vitro can be ascribed to their property of partially counteracting the depression of cell-mediated cytotoxicity that follows exposure to HTLV-I. In the light of data previously and herein described, it seems that alpha- and beta-IFN can be considered potential candidates to define combined therapy with antiviral drugs, to control the early stages of retrovirus-associated disease in human pathology.
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PMID:Role of biological response modifiers in immunochemotherapy of solid tumors and retroviral-induced leukemia. 170 53

It has been demonstrated that the liver loses its capacity to metabolise and eliminate drugs during viral infection or during the operation of host defence mechanisms. This loss in drug metabolism is due to the loss of the cytochrome P-450 component of the mixed function oxidase (the enzyme system primarily responsible for the oxidation of drugs, carcinogens and certain classes of endogenous substances such as steroids, fatty acids and prostaglandins). At present we have identified interferon and factors such as interleukin-1, interleukin-6 and tumour necrosis factor, released from Kupffer cells, as major mediators of the loss. The depression that occurs during viral infection is mediated via the production of interferon. This action of interferon requires the synthesis of an intermediate/s yet to be identified. The molecular mechanism for the decrease in cytochrome P-450 mediated drug metabolism during episodes of viral infections is caused by an interferon-mediated loss in mRNA and subsequent cytochrome P-450 synthesis in the liver.
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PMID:Alteration of drug biotransformation by interferon and host defence mechanism. 170 43


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