ISSN:0892-3973    

DOI:10.3109/08923979509019748

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractA serum free lymphokine preparation derived from human buffy-coat mononuclear cells [buffy coat interleukins (BC-IL)], also named Leukocyte Interleukin, Inj. (LI), trade name Multikine™, containing glycosylated interleukin-2 (IL-2) among other interleukins, was tested in three head and neck cancer patients. They responded with tumor regressions associated with increased tumor infiltration of lymphocytes and tumor cell lysis indicating an LI Interleukin-2 induced tumor-specific immune response. to determine whether these responses elicited by LI were IL-2 driven, augmentation of natural killer cells (NKC) and cytolytic T cells (CTL), was tested bothin vitroandin vivo. A single intraperitoneal (ip) injection of LI in adult BALB/c mice at doses of 3, 10, 30 and 100 of IL-2 equivalence International Units per mouse, led to significant (psubcutaneous(sc). Significant (p<0.05 to<0.01) NKC cytotoxicity was achieved by all four routes.In vitroincubation of murine splenocytes with 30 and 100 International Units/ml (IU/ml) of IL-2 equivalent elevated NKC cytotoxicity significantly (p<0.01) at all effector to target cell ratios tested and exceeded the response achieved with rhIFNy. NKC cytotoxicity of human peripheral blood lymphocytes (HPBL) against the K562 human tumor cell was also significantly elevated (p<0.01) at the 30 and 100 IU/ml doses and (p<0.05) at 3 and 10 IU/ml doses. of particular interest was the significant increase of CTL response in HPBL generated by LI. Significant activity (p<0.01) was achieved with levels of 10, 30 and 100 IU/ml at effector to target cell ratios as low as 6 to 1. These results indicate that the LI containing IL-2 led to the significant increase in NKC and CTL cytolytic activities. Relatively lower doses of LI were needed to attain equivalent cytolytic activities as achieved with rhIL-2 or rhIFNy.

ISSN:0892-3973    

DOI:10.3109/08923979509019749

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractSuperoxide and its derived active oxygen species are responsible for the polymorphonuclear leukocyte (PMN)-mediated tumoricidal activity which is typically shown in the intraperitoneal administration of OK-432, a biological response modifier, for cancer ascites. We examined the effects of intraperitoneal administration of OK-432 with or without syngeneic serum on superoxide generation from PMNs which migrated in the peritoneal cavity using the new method of Cypridina luciferin analog-dependent chemiluminescence for the detection of superoxide. PMNs harvested from rat peritoneal cavity 6 h after the intraperitoneal administration of OK-432 (0.25KE/kg, or 2.5KE/kg) generated larger amounts of superoxide than those harvested after intraperitoneal injection of oyster glycogen (75mg/kg) when stimulated by opsonized zymosan or phorbol myristate acetate. Simultaneous intraperitoneal administration of OK-432 and syngeneic serum induced a greater increase in PMN superoxide generation than OK-432 alone, which was reversed by a complement activation inhibitor (MX-1). Simultaneous injection of OK-432 and heat-inactivated syngeneic serum did not exhibit a significant increase in PMN superoxide generation as compared with OK-432 alone. These results provide pharmacological evidence to the satisfactory therapeutic effects of the intraperitoneal administration of OK-432 with or without serum for patients with cancer ascites, and indicate that complements, in particular C5a, are involved in this enhanced PMN-derived superoxide generation induced by the simultaneous injection of OK-432 and serum.

ISSN:0892-3973    

DOI:10.3109/08923979509019750

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractStreptolysin O, a thiol-activated exotoxin from group Aβ-haemolytic streptococci, caused a dose-dependent depression of aniline hydroxylase, aminopyrine N-demethylase and ethylmorphine N-demethylase activities when added into the hepatic microsomal mixtures from male rats at concentrations 0.02 -0.4 HU/mLin vitro. the activities of 7-ethoxycoumarin O-deethylase, 7-ethylresorufin O-deethylase and 7-pentylresorufin O-depentylase were not altered with the used concentrations of the toxin. Specific antibody against haemolytic action of streptolysin O added to incubation mixturesin vitrowas not able to protect streptolysin-sensitive monooxygenases from the inhibition. the addition of streptolysin 0 (0.01 -0.8 HU/mL) into the cytosol-containing medium did not significantly influence the activity of procainamide N-acetyltransferase. Immunomodulators picibanil (OK 432) and human recombinant interferonα2A which are known to suppress oxidative metabolismin vivoin humans and animals, were without effect either on the cytochrome P-450-dependent monooxygenases or on the N-acetyltransferase activity when administeredin vitroat the doses real in their clinical application (0.001 -0.1 KE/mL of picibanil and 10 -500 U/mL ofα-interferon).

ISSN:0892-3973    

DOI:10.3109/08923979509019751

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractIn an effort to examine the effects of calcium blockers and adenosine on superoxide, hydrogen peroxide, and nitrite secretions by mouse peritoneal macrophages, we have utilized the phenol red method, the superoxide dismutase-inhibitable reduction of ferricytochrome c method, and the Griess reagent method to test products after treating periodate-elicited mouse peritoneal macrophages with verapamil, nifedipine, and adenosine. the results show that after treating the macrophages with chemicals 10 minutes before adding PMA (100 ng/ml), all three chemicals inhibited superoxide (O2) and hydrogen peroxide (H2O2) secretions dose-dependently, yet they failed to suppress macrophage reactive oxygen intermediates (ROI) after a 24 hour treatment. On the other hand, calcium blockers, verapamil and nifedipine, could reduce nitrite secretion (NO2), while adenosine did not show the ability to inhibit NO2. This indicates that calcium, as a secondary messenger, is important for the production of ROI and RNI. the reason behind the loss of the ability to suppress macrophage ROI production in a 24 hour treatment remains unexplored.

ISSN:0892-3973    

DOI:10.3109/08923979509019752

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractThe effects of prostaglandins on superoxide generation by neutrophils were investigated, since these arachidonic acid metabolites are both involved in the early phase of the inflammatory process and during later stages of neutrophil function. Preincubation of these cells for five minutes with concentrations of PGE2 ranging from 10−7to 10−4M was able to significantly reduce superoxide production in PMA-stimulated neutrophils. Other pro-inflammatory PGs tested, such as PGE1α, PGF2α, PGF2α, inhibited the respiratory burst. the PGE2-induced inhibition was compared to that exerted by staurosporine, a PKC inhibitor. the effects of the two drugs were not additive, since the combinations of PGE2and staurosporine reduced O2production to the same extent as staurosporine alone. Possible interferences between PKA-and PKC-mediated transduction signals are discussed.

ISSN:0892-3973    

DOI:10.3109/08923979509019753

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractMethionine enkephalin (Met-Enk) was evaluated for efficacy as an immune activator and potential therapeutic agent in influenza A/NWS/33 (H1N1) viral infections in female BALB/C mice. Influenza infection was induced intranasally with an approximate 90% lethal dose of virus and mice were treated intraperitoneally with doses of 10, 3 and 1 mg/kg/day, with treatments given 24 h pre-, 24 h post-and 72 h post-virus exposure. Splenocytes were assayed for natural killer cell (NK) and cytotoxic T lymphocyte (CTL) activity at time periods 76, 96 and 120 h post virus exposure. the 10 mg/kg dosage level significantly increased both CTL and NK activity at all time periods assayed. Other treatment schedules included single doses of 20, 10 and 3 mg/kg/day Met-Enk at either 24 h post-or 72 h post-virus exposure, with highly significant increases in NK and CTL activity noted after the latter treatment. the results of this study demonstrate the immunomodulatory effects of Met-Enk on NK and CTL in influenza infected mice and suggest a potential for therapeutic applications.

ISSN:0892-3973    

DOI:10.3109/08923979509019754

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractTacrolimus (FK 506) has synergistic immunosuppressive effects in combination with corticosteroids. A steroid dose-lowering effect can be explained partly by the inhibition by FK 506 of cytochrome P-450 III A, which metabolizes corticosteroids. We investigated the influence of combinations of FK 506 and methylprednisolone (MPL) on the suppression of in vitro human lymphocyte proliferation. to quantify the type of drug interaction (synergistic, additive, and antagonistic), three methods (Drewinko's statistical analysis, median-effect principle, and normal distribution model) were used. the interaction appeared synergistic in most combination ratios, but the extent of synergism varied depending on the quantitative method. There may be optimal combination ratios of FK 506 and MPL which achieve more effective immunosuppressive effects.

ISSN:0892-3973    

DOI:10.3109/08923979509019755

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractIn 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-αwere within normal ranges, whereas interferon-γserum 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.

ISSN:0892-3973    

DOI:10.3109/08923979509019756

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractTo test the effect of purified polyunsaturated fatty acids on immune cells in vitro, human peripheral blood mononuclear cells and murine spleen cells were incubated in Opti-MEM medium without serum or even albumin and with 2-mercapto-ethanol, insulin, transferrin and selenium as supplements. the human cells were stimulated with phytohemagglutinin and the murine cells were stimulated with Concanavalin A or lipopolysaccharide. Both human and murine cells were stimulated with recombinant human interleukin-2 to generate lymphokine activated killer cells Linoleic and linolenic acids inhibited all of the immune responses tested, whereas docosahexaenoic and eicosapentaenoic acids did not Similar effects were observed with cultured B16 F10 murine melanoma cells. Mixtures of linoleic and docosahexaenoic or eicosapentaenoic acids also inhibited the mitogenic response to phytohemagglutinin. Inhibition of lipid mediator production by indomethacin, quercetin, rutin, or nordihydroguariaretic acid, and addition of vitamins C and E with anti-oxidant activity failed to reverse the effects of linoleic acid. Thus, linoleic and linolenic acids appear to directly inhibit immune and tumor cells, at least under these conditions

ISSN:0892-3973    

DOI:10.3109/08923979509019757

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor