Showing papers in "Immunopharmacology and Immunotoxicology in 1995"
TL;DR: The results suggest that selective cytotoxicity of TCS to human macrophages/monocytes may be implicated in anti-HIV activity, and that selectively killing some leukemia-lymphoma cells by TCS merit further evaluation in treatment of some lymphoma and leukemia.
Abstract: Trichosanthin (TCS) is a ribosome-inactivating protein from root tubers of Trichosanthes kirilowii Maxim. In this paper, the effects of TCS on the viability of human peripheral blood immunocytes, on the proliferation of lymphocytes, and its cytotoxicity to twelve cell lines of lymphoma or leukemia had been observed. TCS at high concentration (>12.5 μg/ml) affected the viability of human B lymphocytes, but not that of human peripheral blood mononuclear cells (PBMCs), T lymphocytes and granulocytes. Human peripheral blood-derived monocytes/macrophages were hrghly sensitive to TCS (ID50 at 1.70 μg/ml). TCS suppressed lymphocyte proliferation stimulated by Concanavalin A (Con A) or lipopolysaccharide (LPS). Human T cell lines and macrophage cell lines were more sensitive (ID50 < 0.9 μg/ml) to TCS than B cell lines and myeloid lines. These results suggest that selective cytotoxicity of TCS to human macrophages/monocytes may be implicated in anti-HIV activity, and that selectively killing some leukemia-...
89 citations
TL;DR: The data suggest a significant beneficial effect of captopril in Lewis rat EAE, and other inhibitors of ACE or of other peptidases with immune, inflammatory or BBB role, may identify potentially valuable immunopharmacologic agents.
Abstract: Angiotensin converting enzyme (ACE)1 mediates inflammation, participates in T cell stimulation by certain antigenic peptides, and influences the permeability of the blood brain barrier (BBB). ACE is elevated in multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS), characterized by increased BBB permeability. ACE inhibitor captopril suppresses certain immune functions and inhibits inflammatory or autoimmune diseases. We studied the effect of captopril on Lewis rat EAE, an animal model of MS. Fourteen rats with EAE were treated with captopril 30 mg/kg daily from immunization to day 21 post-immunization, and compared with 14 untreated rats. Severity scores and lymphocyte reactivity to myelin basic protein and mitogen were measured. There was a statistically significant (p < 0.05) difference between the mean and cumulative clinical scores of captopril-treated and untreated animals. Lymphocytes from captopril treated EAE rats at the peak of disease severity had diminished responses to MBP and concanavalin A. The data suggest a significant beneficial effect of captopril in Lewis rat EAE. Further studies including other inhibitors of ACE or of other peptidases with immune, inflammatory or BBB role, may identify potentially valuable immunopharmacologic agents.
64 citations
TL;DR: The results indicate that the oral administration of TJ-41 into the tumor bearing mice may be able to enhance concomitant antitumor immunity through the augmentation of the cytostatic activity.
Abstract: The oral administration of a kampo herbal medicine, Hochu-ekki-to (TJ-41: Bu-Zhong-Yi-Qi-Tang) using a water-supplying bottle resulted in a slight but significant inhibition of Meth A growth. The oral administration of TJ-41 with gastric gavage significantly enhanced the specific antitumor activity against Meth A at rechallenge on day 9. In a tumor-neutralizing assay, the tumor draining LN cells of the TJ-41 administered mice showed an antitumor activity against Meth A. In a cytolytic assay, the anti-Meth A specific cytolytic T lymphocyte activity was not detected in the spleen cells of the Meth A bearing and TJ-41 administered mice. The oral administration of TJ-41 enhanced the natural killer (NK) activity of the spleen cells in naive mice but could not improve the decreased NK activity of spleen cells from the tumor bearing mice. In a cytostatic assay, the peritoneal exudate cells from the Meth A bearing and TJ-41 administered mice showed a significantly higher amount of cytostatic activity against Meth A than that from either Meth A bearing or TJ-41 administered mice. These results indicate that the oral administration of TJ-41 into the tumor bearing mice may thus be able to enhance concomitant antitumor immunity through the augmentation of the cytostatic activity.
43 citations
TL;DR: A condition of peripheral immune depression in cHCV patients with an exaggerated shedding of various mediators endowed with noxious effects for the host is indicated.
Abstract: 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-α were within normal ranges, whereas interferon-γ 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 monocy...
35 citations
TL;DR: It is concluded that the sexual dichotomy in spontaneous autoimmune models is due to protective effects of androgens and that the mortality by estrogens isdue to toxic effects rather than accelerated autoimmunity.
Abstract: Sex hormones affect (auto)immune responses in various ways Investigations of the effects of estrogens have produced contradictory results We studied the effects of gender, gonadectomy and of (supra)physiological doses of (the orally active) ethinylestradiol (EE) in two spontaneous autoimmune disease models: the NZB/NZW F1 and NOD mice In both models we confirmed the female preponderance and the aggrevating effects of gonadectomy in males but not in females The accelerated mortality found in NZB/W mice treated with supraphysiological doses of EE was not associated with increased proteinuria, increased IgG-type anti-DNA levels or increased mononuclear cell infiltrations in the submandibular gland In contrast, we found a severe reduction in body weight and in the weights of various organs (indications of toxicity), and a decrease rather than an increase in proteinuria and in mononuclear cell infiltrations (indications for autoimmunity) Physiological doses of EE did not significantly affect disease symptomsIn the NOD model a near-physiological, non-toxic dose of EE did not cause consistent changes on immunological disease symptoms either Therefore, we conclude that the sexual dichotomy in spontaneous autoimmune models is due to protective effects of androgens and that the mortality by estrogens is due to toxic effects rather than accelerated autoimmunity
32 citations
32 citations
TL;DR: It is indicated that the treatment with IVIG is an effective and safe tool for suppressing the recurrences of genital HSV infections and a trend is found indicating IVIG as more effective in reducing the viral load.
Abstract: Effective treatment is not currently available for suppressing the recurrence of genital herpes simplex virus (HSV) infections. Since intravenous immunoglobulins (IVIG) proved useful against HSV in experimental models, we treated patients with very high frequency of HSV genital recurrences (more than 15 episodes per year) with IVIG (400 mg/Kg every fourth week). The control group was treated with intermittent oral acyclovir (800 mg twice a day for one week every month). Both groups were treated for six months and, then, patients were followed-up to further six months. Both IVIG and acyclovir were effective in reducing the frequency of HSV genital recurrences as compared to base-line. However, patients treated with IVIG had a more striking reduction in the frequency of recurrences as well as both a shorter mean duration and a minor severity of the lesions as compared to acyclovir-treated patients. Furthermore, we found a trend indicating IVIG as more effective in reducing the viral load. Since in IVIG-recipients we found a strong increase of peripheral blood lymphocytes with natural killer (NK) surface phenotype, we suggest that the clinical effectiveness of IVIG treatment is probably mediated via the expansion of NK cell populations. Our study indicates that the treatment with IVIG is an effective and safe tool for suppressing the recurrences of genital HSV infections.
27 citations
TL;DR: It is suggested that trichothecene mycotoxins may be immunosuppressive by affecting viability, adherence and phagocytic potential of mononuclear phagcytic cells of young turkeys.
Abstract: Macrophage cells isolated from the abdominal cavity of 21-day-old turkeys after a single injection of Sephadex suspension were used to quantitate the effects of direct in vitro exposure to deoxynivalenol (DON), 3-acetyldeoxynivalenol (3ac-DON), scirpentriol (STO), or 15-acetylscirpenol (15-MAS). Macrophage monolayers were established on glass surfaces and cells were exposed to graded levels of individual mycotoxins for 1 hour: DON, 20 -640 μ9/μ1 of culture; 3ac-DON, STO, 15-MAS, 20 -1280 μg/μ1 of culture. All four mycotoxins caused dose-related effects. A concentration of 50 μg/ml DON caused a significant decrease in macrophage adherence, phagocytosis of opsonized SRBC, and number of opsonized SRBC per macrophage; at 200 μg/ml, phagocytosis of unopsonized SRBC was decreased. There were also increasing percentages of damaged macrophages with increasing DON doses as indicated by morphological alterations. Linear decreases in macrophage viability on exposure to 3-acDON and STO were observed. Moreover...
26 citations
TL;DR: Findings showed that Fusarium toxins alter performance and immune end points in chickens, imply that chickens exposed to mycotoxins may be more susceptible to infectious diseases.
Abstract: White Leghorn Cornell K-strain chicks (3 replicates of 16 per pen) were started at Day 7 on feed amended with Fusarium proliferatum culture material containing fumonisin B1, fumonisin B2, and moniliformin at 61, 10.5, and 42.7 ppm, respectively. Observed effects on performance of treated birds included reduced feed conversion at 2 wk, and reduced body weight of males and females up to 6 wk (P < or = .05). Splenic, thymic, and liver weights, normalized for body weight, were reduced (P < or = .05) with no change in bursa of Fabricius. No significant changes were observed histologically in the spleen, bursa, kidney, heart, liver, cecal tonsils, colon, or tibia. Significant suppression in total Ig and IgG levels occurred. Macrophages from treated chicks exhibited a 34% reduction in phagocytic activity. Natural killer cell activity was not affected. These findings, which showed that Fusarium toxins alter performance and immune end points in chickens, imply that chickens exposed to mycotoxins may be more susceptible to infectious diseases.
24 citations
TL;DR: Cal calcium, as a secondary messenger, is important for the production of ROI and RNI, and verapamil and nifedipine, could reduce nitrite secretion (NO2-), while adenosine did not show the ability to inhibit NO2-.
Abstract: In 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 re...
19 citations
TL;DR: The immunomodulatory effects of Met-Enk on NK and CTL in influenza infected mice are demonstrated and a potential for therapeutic applications is suggested.
Abstract: Methionine 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.
TL;DR: The 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.
Abstract: The 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 10−7 to 10−4 M 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 PGE2 and staurosporine reduced O2 production to the same extent as staurosporine alone. Possible interferences between PKA-and PKC-mediated transduction signals are discussed.
TL;DR: The racemate and the two enantiomers of ketamine suppressed FMLP- and zymosan-induced chemiluminescence of PMN in a dose-dependent fashion and did not result from a specific receptor interaction.
Abstract: The effects of the commercially available ketamine preparation (Ketanest), the ketamine racemate and of the two enantiomers, the R(-)-racemate and the S(+)-racemate, as well as its drug-free solvent were examined by N-formyl-methionyl-leucyl-phenylalanine-(FMLP)- and zymosan-induced oxygen radical production of polymorphonuclear cells (PMN). The racemate and the two enantiomers of ketamine suppressed FMLP- and zymosan-induced chemiluminescence of PMN in a dose-dependent fashion to the same extent. Therefore suppression of chemiluminescence of PMN by ketamine does not result from a specific receptor interaction.
TL;DR: A review of the strategies for the development and application of new anti-arthritic agents and their applications in immunopharmacology and immunotoxicology in 1995.
Abstract: (1995). A review on the Strategies for the Development and Application of New Anti-arthritic Agents. Immunopharmacology and Immunotoxicology: Vol. 17, No. 4, pp. 607-663.
TL;DR: Negative correlations between helper/cytotoxic ratio and malondialdehyde levels were obtained in blood and spleen during iron administration, which supports the hypothesis that lipid peroxidation plays a role in the immunological abnormalities observed in experimental hemosiderosis.
Abstract: This study was undertaken to investigate the hypothesis that lipid peroxidation might be associated with immunological abnormalities in experimental hemosiderosis. The correlation between the degree of plasma and spleen lipid peroxidation with lymphocyte proliferative response and with the proportion of T lymphocyte subsets was studied in normal and iron overloaded male Sprague Dawley rats. The iron-loading protocol consisted of a total dose of iron-dextran (1.5 mg/Kg body weight) divided in daily i.m. injections over twenty consecutive days. Lipid peroxidation was measured by the thiobarbituric acid assay in plasma and in homogenates of spleen. Plasma lipid peroxide level increased rapidly after i.m. administration of iron-dextran and decreased sharply at 48 h after the last injection. Conversely, a progressive increase of lipid peroxidation in homogenates of spleen was observed in the course of the iron overload protocol, remaining high even at 50 days after initiation of iron-dextran injections. The increase of spleen lipid peroxide levels was associated with decreased lymphocyte proliferative response to Con A in iron overloaded rats. The addition of superoxide dismutase and catalase to lymphocyte cultures reversed the inhibition of the proliferative response, implicating reactive species of oxygen as the causative agents of these alterations. These effects may be related with the enhanced membrane and DNA damage occurring during intracellular and extracellular peroxidation. Negative correlations between helper/cytotoxic ratio and malondialdehyde levels were obtained in blood and spleen during iron administration. These results supports the hypothesis that lipid peroxidation plays a role in the immunological abnormalities observed in experimental hemosiderosis.
TL;DR: The results suggest that the inhibitory effect of the isoferritins on lymphocyte proliferative response is due, at least partially, to the iron content of this protein and not exclusively to variation in pI as suggested by other authors.
Abstract: Iron and ferritin impair a variety of immunological functions. To evaluate the effect of ferritin iron content on rat lymphocyte proliferative response, isoferritins that differ in their iron content and isoelectric point (pI) were isolated from iron overload rat livers by ultracentrifugation (isoferritins with high iron content and low pI) or crystallization (isoferritins with low iron content and high pI) methods. Additionally, commercial horse splenic ferritin (with a lower pI and higher iron content than rat isoferritins) was also tested. Proliferative response to Con A was decreased in a dose-dependent manner in all assays in which spleen cells were incubated with rat and horse isoferritins. However, isoferritins with higher iron contents (rat isoferritin obtained by ultracentrifugation and horse ferritin) caused a greater decrease of proliferative response at 5 and 25 micrograms/ml than the others. Rat and horse apoferritins showed no inhibitory effect on lymphocyte proliferative response, suggesting that the effect is due to iron probably through the damaging effect of reactive oxygen species generated by iron released by the isoferritins on lymphocyte functions. Additionally, the role of serum ferritin level on proliferative response was studied in an experimental model of iron overload in rats. An inverse relationship between the proliferative response and serum ferritin levels was observed. Our results suggest that the inhibitory effect of the isoferritins on lymphocyte proliferative response is due, at least partially, to the iron content of this protein and not exclusively to variation in pI as suggested by other authors. These results are in agreement with the possible immunosuppressor role of ferritin in vivo.
TL;DR: The immunotoxic effect, determined as mitogenic activation of leucocytes by phytohemagglutinin, concanavalin A and lipopolysaccharide, was detected at 10 to 100-fold lower concentrations of p-chloroaniline than those which resulted in toxic effects.
Abstract: Toxic and immunotoxic effects of p-chloroaniline-a metabolite of herbicide monolinuron-were investigated in peripheral blood leucocytic suspensions of five sheep using a migration-inhibition test. The toxic effect of p-chloroaniline was recorded at concentrations 1.0 to 0.1 mg.ml−1 and the immunotoxic one at concentrations 0.01-0.001 mg.l−1. The toxic effect was demonstrated by total inhibition of leucocyte migration. The immunotoxic effect, determined as mitogenic activation of leucocytes by phytohemagglutinine, concavaline A and lipopolysaccharide, was detected at 10 to 100-fold lower concentrations of p-chloroaniline than those which resulted in toxic effects.
TL;DR: Some novel LPG-mediated escape mechanisms of promastigotes from human phagocyte responses, such as the impairment of oxidative burst and of chemotactic activity are emphasized.
Abstract: Protozoan parasites of the Leishmania genus are the causative agents of important diseases in humans and animals. During their life cycle in vertebrate hosts, protozoa are able to live and proliferate within phagolysosomes of host phagocytic cells. The capacity to live in this hostile environment is likely due to the cell surface glycoconjugate expression. In particular, lipophosphoglycan (LPG), a major surface glycoconjugate of Leishmania promastigotes, has been reported to play an active role in protecting parasites within phagolysosomes via the impairment of killing mechanisms. In this review, the authors emphasize some novel LPG-mediated escape mechanisms of promastigotes from human phagocyte responses, such as the impairment of oxidative burst and of chemotactic activity. In the light of these findings, the knowledge of biological actions of LPG may be useful in order to prepare a vaccine against human leishmaniasis, using LPG defective avirulent mutant strains.
TL;DR: Results indicate a direct influence of the nervous system on natural immune cytotoxic functions in rats by using the neurotoxin capsaicin, which interferes with the synthesis and intraneuronal transport of peptides.
Abstract: The direct and indirect interactions between the nervous system and its transmitters with NK cell cytotoxic functions has been evaluated in the rat by using the neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). When administered to neonatal rats, capsaicin (50 mg/Kg in 10% ethanol and 10% tween 80 at 2 days of age) interferes with the synthesis and intraneuronal transport of peptides by causing irreversible degeneration of c fiber afferent nerves.Capsaicin treatment resulted in a marked inhibition of NK and ADCC activities both in the spleen and peripheral blood. Inhibition was already evident on day 15 after treatment and persisted until day 90 in the spleen; at this time NK cytotoxicity in the peripheral blood returned to control levels.The inhibitory effect of capsaicin treatment on peripheral blood NK and ADCC activities was associated with changes in NK cell number evaluated as percentage of cells with an LGL morphology and expressing the NK-RP1 cell surface receptor. LGL numbers did n...
TL;DR: In this article, treatment of AIDS with drugs targeted to Inhibit Different Stages of the HIV Life Cycle is described. But the authors do not discuss the effects of these drugs on the human body.
Abstract: (1995). Treatment of AIDS with Drugs Targeted to Inhibit Different Stages of the HIV Life Cycle. Immunopharmacology and Immunotoxicology: Vol. 17, No. 2, pp. 217-245.
TL;DR: Guinea pigs treated with S-ethylthiotrifluoroacetate developed anti-TFA antibodies, and following exposure to halothane exhibited an enhanced antibody response, indicating that enhancement of the humoral immune response does not appear to be sufficient for production of Halothane hepatitis.
Abstract: Halothane hepatitis appears to result from an inappropriate immune response to the products of halothane metabolism. Attempts to produce an animal model for halothane hepatitis have been largely unsuccessful. Although guinea pigs produce neoantigens following treatment with halothane, the subsequent antibody response is weak, possibly accounting for the failure to produce halothane hepatitis in these animals. In order to increase the antibody response to halothane neoantigens, three methods for trifluoroacetylating proteins were used. Guinea pigs were either treated with S-ethylthiotrifluoroacetate, autologous lymphocytes trifluoroacetylated ex vivo, or immunized with trifluoroacetylated mycobacterial protein, followed by exposure to halothane, and examined for anti-halothane metabolite antibodies (anti-TFA antibodies). Animals treated with S-ethylthiotrifluoroacetate developed anti-TFA antibodies, and following exposure to halothane exhibited an enhanced antibody response. Treatment with trifluoroacetylated lymphocytes also resulted in an enhanced anti-TFA antibody response following halothane exposure. Immunization with trifluoroacetylated mycobacterial proteins resulted in very high anti-TFA antibody titers. However, subsequent exposure to halothane had no observable effect on specific antibody titers. Exposure to halothane, regardless of treatment, resulted in the production of anti-microsomal protein antibodies. Signs of halothane hepatitis were not observed, indicating that enhancement of the humoral immune response does not appear to be sufficient for production of halothane hepatitis.
TL;DR: Linoleic and linolenic acids appear to directly inhibit immune and tumor cells, at least under these conditions, as observed with cultured B16 F10 murine melanoma cells.
Abstract: To 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.
TL;DR: It is suggested that cocaethylene modulates relatively early events following T cell stimulation probably related to the interleukin-2 system.
Abstract: This report describes the response of normal human T cells to stimulation in vitro in the presence of nano-micromolar concentrations of cocaethylene. Thymidine incorporation by concanavalin A-stimulated peripheral blood mononuclear cells was generally blunted by cocaethylene, albeit to different degrees depending upon the donor tested. the formation of concanavalin A-induced blast cells was decreased by increasing concentrations of cocaethylene. the production of interleukin-2 was also blunted in a dose-dependent fashion by cocaethylene, and this outcome was more consistently observed in stimulated peripheral blood mononuclear cells, compared to unseparated whole blood preparations. An inverse dose dependence was obtained in relation to the response of blast cells to recombinant human interleukin-2 in the presence of cocaethylene. These lines of evidence, taken together with our preliminary studies aimed at testing the effect of cocaethylene on the expression of certain membrane markers of activat...
TL;DR: The interaction appeared synergistic in most combination ratios, but the extent of synergism varied depending on the quantitative method, suggesting there may be optimal combination ratios of FK 506 and MPL which achieve more effective immunosuppressive effects.
Abstract: Tacrolimus (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 IIIA, 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.
TL;DR: The data indicate that serotonin and its antagonists interfere directly with mitosis and/or autocrine stimulation of target cells.
Abstract: Blastogenic transformation of murine spleen cells elicited with concanavalin A was suppressed by serotonin 10(-12) to 10(-6) M, and marginally stimulated by its antagonists ketanserin and propranolol in low concentrations (10(-15) to 10(-11) M). Ketanserin (5-HT2 receptor ligand) and propranolol (5-HT1A and beta-adrenergic ligand) did not block the suppressive effect of serotonin if used along with it in equimolar concentrations (10(-9) M). Ergot-alkaloid dihydroergosine suppressed, whereas dihydroergotoxin stimulated the blastogenic transformation. Opposite effects of the agents were obtained in experiments with mouse myeloma X63/Ag 8.653 and hybridoma SHV 125 cell lines, which unlike normal lymphoid cells, are homologous cell populations and proliferate spontaneously. The data indicate that serotonin and its antagonists interfere directly with mitosis and/or autocrine stimulation of target cells.
TL;DR: Effects on host defenses of Total Parenteral Nutrition with long- (LCT) and medium-chain triglycerides (MCT) were studied and survival to lipopolysaccharide challenge, blood clearance of E. coli, in vivo and in vitro production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were investigated.
Abstract: Effects on host defenses of Total Parenteral Nutrition (TPN) with long-(LCT) and medium-chain triglycerides (MCT) were studied.Survival to lipopolysaccharide (LPS) challenge, blood clearance of Escherichia coli, in vivo and in vitro production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were investigated.In BALB/c mice, LCTs produced a 25% reduction in mortality, compared with controls. TPN performed with a LCT plus MCT mixture reduced mortality by 50%. Spasms appeared after 18 h and 12 h respectively in mice treated with LCT-MCT mixture or LCTs alone, respect to controls (8 h). The LCT-MCT mixture produced a 67% blood clearance of E. coli after 1 h, while the treatment with LCTs alone had no significant effects compared to controls (about 40%). The LCT-MCT mixture induced a 50% increase in chemiluminescence respect to controls. A 33% increase was observed in rats treated with LCTs alone. TNF-α serum levels after challenge with LPS were not modified by any of the triglycerides or t...
TL;DR: The results show that antitumor active vaccination, using sized liposomes as adjuvants, induces an antitumors host response and a significant inhibition of tumor progression.
Abstract: Immunization of C57BL/6 mice with tumor-derived membrane-proteins encapsulated in sized liposomes (0.2 μg/mouse) and composed by phosphatidylcholine or sphingomyelin, significantly reduced the mean values of spontaneous lung metastasis from both B16 (0.7 ± 0.5 and 1.2 ± 0.6, respectively) and 3LL (4.8 ± 2.5 and 7.2 ± 4.1, respectively) tumors, with respect to control (HEPES) groups (4.8 ± 1.1 and 19.0 ± 4.4, respectively). However, no significant antimetastatic effect was observed using free tumor-derived proteins (2 μg/mouse) or liposome vehicle alone. Specific humoral immune response after the vaccination was studied by flow cytometry of tumor cells incubated with a pooled sample from each group of immunized mice and FITC-conjugate antimouse immunoglobulins. The results showed that the highest number of positive tumor cells was identified using sera from immunized mice with sized liposomes encapsulating tumor-derived proteins whereas the immunization with the protein fraction in free form failed...
TL;DR: The data suggest that the RA potentiating effect is the result of an increase in stimulator cell immunogenicity after their pre-treatment with RA before use in MLR.
Abstract: The effects of two retinoids, all-trans-retinoic acid and 13-cis-retinoic acid on murine splenic lymphocyte proliferative response in mixed culture were evaluated. In contrast with previously reported absence of retinoic acid (RA) effect on mixed lymphocyte reaction (MLR) the conditions for a strong potentiation of proliferative response of murine lymphocyes with RA were obtained. Stimulatory cells were determined to be the main targets for RA. The data suggest that the RA potentiating effect is the result of an increase in stimulator cell immunogenicity after their pre-treatment with RA before use in MLR. Optimal potentiation by retinoids of proliferative response was found at non-optimal conditions of mixed culture.
TL;DR: Findings indicate that the diacetate ester of PDC/HDC is an effective hyposensitizer to poison ivy urushiol, and that this hyPOSensitization can be reasonably accomplished in a single dose treatment regimen.
Abstract: Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of lmg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of penta-decyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and...
TL;DR: It is suggested that administration of diazepam in vivo plays a role in both the nonspecific and specific immune response, producing in the macrophages a reorganization process of microfilaments.
Abstract: We have investigated the effect of therapeutic doses of diazepam (7 μg/mouse) on the association of actin with the macrophage cytoskeleton using cytochemical and morphological methods.Results obtained indicated that diazepam was able to modulate the content of actin in macrophages; such an effect proved to be time-dependent. After fixation and staining for indirect immunofluorescence with actin antibody, peritoneal macrophages from mice treated for short time with diazepam, showed a fluorescent intensity increase compared to control mice. The fluorescent intensity augmented reaching peak value within 14 days of treatment. Afterwards, this value dropped below control value for mice that underwent longer treatments. In the in vitro experiments concentrations of 10−5 M, diazepam inhibited a well cell spread and a lower amount of actin after 15 min of incubation was also revealed.These results suggest that administration of diazepam in vivo plays a role in both the nonspecific and specific immune resp...