摘要:

AbstractThein vitroeffects of 3′-azido-3′-deoxythymidine (AZT) (at concentrations of 1, 10 and 100µM, respectively) on normal human polymorphonuclear cell (PMN) and monocyte-macrophage hnctional capacities were evaluated. Results show that AZT was able to decrease monocyte phagocytosis only, while PMN polarization, phagocytosis and killing were unaffected by drug pretreatment. Quite interestingly, monocyte-derived macrophages maintained their unaltered phagocytic hnction in spite of the presence of AZT in overnight cultures, thus indicating that monocytes are more susceptible than macrophages to the antiproliferative effects of AZT. Since our data indicate that AZT affects normal human monocyte phagocytosis, it is advisable to evaiuate this immune parameter in HIV+ patients administered with this drug.

ISSN:0892-3973    

DOI:10.3109/08923979609052730

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractSR 31747 is a new sigma ligand which has immunosuppressive properties. The immunopharmacology of SR 31747 was investigatedin vivoby studying its effects on the thymuses of C3H mice. The action of SR 31747 was compared with the reference drugs cyclosporin-A and dexamethasone on the basis of several parameters which were: the thymus weight; the number of thymocytes per organ; the percentages of mature CD4+ or CD8+ thymocytes and of immature CD4+ CD8+ thymocytes. SR 31747 slightly but significantly decreased the thymus weight at the dose of 50 mg/kg whereas the number of thymocytes per organ was significantly decreased from 6.25 mg/kg to the 50 mg/kg dose. It had rather no effect on the percentages of immature and mature subsets. These data led to the conclusion that the effects of SR 31747 on the thymuses of C3H mice were close to those obtained with cyclosporin-A and different from those obtained with dexamethasone.

ISSN:0892-3973    

DOI:10.3109/08923979609052731

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractWhen aged BALB/c mice (∼6 months old) were treated with a Kampo (Japanese herbal) medicine“Sho-seiryu-to (SST)”(1 g/kg, 10 times) orally from 7 days before to 4 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34 (H1N1 subtype) by nasal site-restricted infection, replication of the virus in the broncho-alveolar cavity was efficiently inhibited at 5 days after infection in comparison with water-treated mice. The antiviral IgA antibody in the broncho-alveolar wash of the SST treated aged mice increased significantly. When mice (7 weeks old) were administered orally with SST (1 and 2 g/kg, 7 times) from 4 days before to 3 days after the infection and infected with mouse-adapted influenza virus A/Guizhou/54/89 (H3N2 subtype) or B/Ibaraki/2/85, replication of the viruses in the nasal cavity and lung were significantly inhibited at 4 days after infection in comparison with control mice. When mice infected with influenza virus A/Fukuoka/C29/85 (H3N2) before 14 days were secondary infected with A/PR/8 virus and administered orally with SST (1 g/kg, 5 times) from 2 h to 5 days after the secondary infection, replication of the virus in both nasal and broncho-alveolar cavities were significantly inhibited at 5 days after the secondary infection in comparison with water-treated control. Oral administration of SST (1 g/kg, 18 times) from 7 days before to 14 days after vaccination followed by secondary nasal inoculation of influenza HA vaccine (5µglmouse) at 14 days after the first vaccination significantly augmented nasal antiviral IgA antibody and broncho-alveolar and serum antiviral IgG antibodies. These results suggest that SST is useful for influenza virus infection on aged persons and for cross-protection of subtypes of influenza A viruses and influenza B virus. SST is also useful for the treatment of influenza virus infection on human which has a history of influenza virus infection and/or influenza vaccination.

ISSN:0892-3973    

DOI:10.3109/08923979609052732

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractIn mice bearing immunogenic tumors, adding thymic humoral factor-γ2 (THF-γ2)1immunotherapy as an adjunct to anticancer chemotherapeutic regimens not only potentiates the antitumor activity of each drug but also repairs tumor/chemotherapy-induced damage to T-cell populations and functions. The Lewis lung carcinoma (3LL) is a weakly immunogenic, highly metastatic tumor in C57BL/6 mice. To investigate whether the immunoregulatory octapeptide is also effective against a tumor that does not elicit an antitumor immune response, we assessed the effect of combination THF-γ2 immunotherapy and chemotherapy in 3LL-bearing mice. The results indicate that THF-γ2 combined with either Melphalan or 5-Fluorouracil was more effective in reducing metastatic load than either chemotherapeutic drug alone and was characterized by massive infiltration of lymphatic cells. The combined chemoimmunotherapy treatment also prolonged the survival time in all treated animals and repaired T-cell defects and impairedin vitrocellular immune response parameters, induced either by the tumor or by chemotherapy. THF-γ2 immunotherapy reversed the decrease in the number of bone-marrow myeloid colonies (GM-CFU) induced by chemotherapy treatment of tumor-bearing mice, supporting the hypothesis that THF-γ2 directly stimulates the proliferation of myeloid stem cells. The overall results imply, that when administered as an adjunct to chemotherapy, THF-γ2 immunotherapy is equally effective against immunogenic and nonimmunogenic tumors.

ISSN:0892-3973    

DOI:10.3109/08923979609052733

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractThe role of cytochrome P-450 in the regulation of plasma membrane Ca+2permeability of human peripheral T-lymphocytes by intracellular Ca+2was examined. We assessed the effect of imidazole inhibitors of cytochrome P-450 on the intracytoplasmic free Ca+2([Ca+2]i) response generated using the microsomal ATPase inhibitor thapsigargin (THG) to deplete the intracellular Ca+2stores. Econazole, miconazole and clotrimazole dramatically inhibited the THG mediated increase in [Ca+2]i and indud an increase in [Ca+2]i themselves. This inhibitory effect was previously observed in other cell systems and was attributed to inhibition of cytochrome P-450 by these agents. However, we evaluated a variety of structurally dissimilar P-450 inhibitors and found that none affected [Ca+2]i, indicating that the mechanism of imidazole action does not involve P-450.

ISSN:0892-3973    

DOI:10.3109/08923979609052734

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractThe aim of the liresent study was to investigate putative mechanisms implicated in the impaired phagocytic response of spontaneously hypertensive rats (SHR)1. The effect ofin vitrotreatment with isoproterenol (ISO), aβ-adrenergic drug, on phagocytosis and respiratory burst by splenic macrophages (SpMØ) from normotensive Wistar-Kyoto rats (WKY) and SHR with established hypertension, respectively, was evaluated. Furthermore, the relaxant effect of ISO was determined in phenilephrine-precontracted thoracic aorta strips from SHR compared with age-matched WKY rats. Results indicate that exposure of rat SpMØto ISO generate a significant and dose-dependent reduction of phagocytosis and oxidative burst which was antagonized, almost completely, by theβ-adrenergic antagonist propranolol (PRO). Unlike normotensive, in hypertensive rats treatment with ISO fail to modulate phagocytosis and respiratory burst activity by SpMØ. At vascular level, aortic relaxation by ISO was reduced in SHR when compared to WKY rats. These findings suggest that SHR exhibit changes not only in vascular, but also in macrophageβ-adrenoceptor-mediated responses. It is postulable that sympathetic overactivity could be responsible for impaired phagocytic functions andβ-receptor alterations observed in SHR.

ISSN:0892-3973    

DOI:10.3109/08923979609052735

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractWe have shown previously that Lipopolysaccahride (LPS) can suppress macrophage phagocytosis and that suppression was not mediated by the induction of cytokines (1). In this study we investigated the mechanisms by which LPS may be suppressing phagocytosis in thioglycolate-elicited murine peritoneal macrophages, by evaluating the effect of LPS on various components of the phagocytic machinery. LPS mediated suppressionin vitrowas not due to reduced Fcγreceptor gene expression. LPS-treatment did result in a slight reduction in the number of FcγRI receptors but this reduction could not account for the degree of suppression seen following LPS treatment. LPS treatment altered the distribution of microfilaments and microtubules and Møs with such alterations had reduced phagocytic activity, suggesting that LPS may be suppressing phagocytosis via its effects on the cytoskeletal network. LPS administrationin vivoalso resulted in reduced phagocytic activity.

ISSN:0892-3973    

DOI:10.3109/08923979609052736

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractThe effects of etomidate in an alcoholic vehicle and in a lipid-emulsion as well as those of propofd on N-formyl-methionyHeucyl-phenylalanine (FMLP-) and zymosan-induced oxygen radical poduction of neutrophils were examined and compared with the effects of their respective vehicles. Furthermore free-radical scavenging capacities of these medications were investigated. The doseresponse effects of etomidate, propofol and their respective vehicles on neutrophil function were tested by FMLP- and zymosan-induced chemiluminescence of neutrophils and, in addition, in a cell-free chemiluminescence system. Effects of commercial preparations of etomidate were generally not drug-specific but due to the vehicles and/or to unphysiologic osmolality values. Propofol impaired chemiluminescence of neutrophils in a drug-specific manner, even in the therapeutic concentration range. Free-radical scavenging contributed to this depression ot chemiluminescence of neutrophils by propofol. Different composition of the lipid-emulsions of etomidate and propofol resulted in either a stimulation or suppression of chemiluminescence of neutrophils. Propofol but not etomidate impairs chemiluminescence of neutrophils drug-specifically. Besides a potential interaction with the neutrophils, free-radical scavenging accounts for this suppression.

ISSN:0892-3973    

DOI:10.3109/08923979609052737

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractThe ability of the polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BP) and its metabolites to be immunosuppressive has been well documented by many investigators. The arylamine, 2-aminofluorene (AF) and its metabolic intermediates have not been as widely studied in this regard. Here, we investigate the effect of BP, 3-hydroxy-BP (3-OH-BP), AF, N-hydroxy-AF (N-OH-AF) and acetyl-AF (AAF) on T-cell proliferation using the T-cell mitogen, Concanavalin A (ConA). These compounds as well as BP-7,8-diol-9,10-epoxide (BPDE) were also used to determine their effect on T-cell-mitogen binding. Both AF and BP are substrates for the P-450 and flavin-containing monooxygenase enzyme system, which can be induced withß-naphthoflavone (ßNF). We incubatedßnF with BP and AF to determine the effect of a P-450 inducer on BP and AF mediated-ConA suppression. Here we demonstrate that BP, 3-OH-BP, AF, and AAF are able to suppress the proliferative response to ConA, while N-OH-AF cannot. Further, we show that BP, 3-OH-BP, BPDE, AF and N-OH-AF do not alter the ability of ConA to bind the mitogen receptor of splenic T-cells, indicating an intracellular mechanism for suppression. Studies withßNF indicate that this P-450 inducer enhances the anti-proliferative effect of BP, while it abolishes this effect of AF.

ISSN:0892-3973    

DOI:10.3109/08923979609052738

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractIn order to determine the effects of halothane on rat cell-mediated immune function, rats were exposed to 1% halothane for up to 5 hours. Immediately, 24 hours or 48 hours following anesthesia, rat lymphocytes from the spleen were analyzed for their ability to respond to the mitogens phytohemagglutinin (PHA), pokeweed mitogen (PWM), concanavalin A (ConA) and lipopolysaccharide (LPS). In addition, percentages of lymphocyte subpopulations in the spleen were assessed as well as ability of the lymphocytes to express specific receptors. Extended periods of halothane anesthesia (5 hours) suppressed the ability of the lymphocytes to respond to the mitogen PHA immediately following anesthesia. Twenty-four hours later, proliferative responses to the mitogens PHA, PWM and ConA were significantly reduced. However, by 48 hours following treatment, proliferative responses were normal. Halothane did not alter proliferative responses to the mitogen LPS. Prolonged anesthesia (5 hours) also increased the percentage of T and CD8+ (cytotoxic) lymphocytes in the spleen, although for less than 24 hours. The ability of T lymphocytes to express both the CD8 and CD25 (IL-2) receptors in response to PHA were suppressed. These results suggest that halothane suppresses rat T cell function, perhaps through suppression of IL-2 receptor expression.

ISSN:0892-3973    

DOI:10.3109/08923979609052739

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor