摘要:

AbstractImmunization of C57BL/6 mice with tumor-derived membrane-proteins encapsulated in sized liposomes (0.2μg/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 (2μg/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 to induce this effect. In addition, an increased cytotoxicity towards 3LL and B16 tumor cells can also be observed when tumor cells were incubated with spleen effector cells plus specific immunosera. In conclusion, our results show that antitumor active vaccination, using sized liposomes as adjuvants, induces an antitumor host response and a significant inhibition of tumor progression.

ISSN:0892-3973    

DOI:10.3109/08923979509016379

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractInvestigative attempts to identify novel therapy for inflammatory connective tissue diseases continue to evolve. Amiphlose hydrochloride (amiprilose HCl) is a synthetic carbohydrate shown to have anti-inflammatory effects in animal models of inflammatory arthritis and in a multicenter clinical trial. Interleukin-1 (IL-1) is an important mediator of immune regulation, inflammation and joint destruction in arthritis. In the present study, the effects of amiprilose HCI on IL-1 activity, production and receptor distribution were investigated. Drug effects on IL-2 production and receptor distribution on lymphocytes were also explored. Potential regulation of IL-1 activity was determined by monitoring the effects of amiprilose HCl on IL-1 stimulated proliferation of murine thymocytes and human synovial cells. Inhibitory effects on IL-1ßand IL-2 production by stimulated human peripheral blood monocytes were measured by ELISA and lymphocyte IL-1ßand IL-2 receptor distribution were analyzed by flow cytometry. The results from in vitro studies demonstrated that low concentrations of amiprilose HCI (1-100μg/ml) stimulated thymocyte proliferation and enhanced the proliferative response of IL-1 stimulated human synovial fibroblasts. IL-1ßproduction in cultures of human peripheral blood monocytes was significantly decreased after exposure of the cultures to varying doses of amiprilose HCl as determined by ELISA. Exposure of mitogen activated human peripheral blood lymphocytes to amiprilose HCl resulted in decreased IL-2 production at high concentrations of drug as compared to control. However, at doses of amiprilose HCI previously found to stimulate thymocyte proliferation (1-10μg/ml), increased levels of culture supernatant IL-2 were observed. No amiprilose HCl mediated changes in lymphocyte IL-1ßor IL-2 receptor expression were observed. The regulatory effects of amiprilose HCl on cytokines support the potential of this drug as a therapeutic agent for the treatment of inflammatory arthritis.

ISSN:0892-3973    

DOI:10.3109/08923979509016380

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractThe anti-tumour antibiotic Bleomycin, the experimental immunostimulatory tripeptide FK 565, and the immunosuppressive agent Cyclosporin A were examined for theirin vitroeffects on the release of the haemopoietic cytokine Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) from LPS stimulated BALB/c adherent peritoneal macrophages. FK 565 and Bleomycin produced an increase in GM-CSF release indicating that these agents are capable of stimulating peritoneal macrophage populations. Cyclosporin A was found to have no effect.

ISSN:0892-3973    

DOI:10.3109/08923979509016381

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractAngiotensin converting enzyme (ACE)1mediates 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.

ISSN:0892-3973    

DOI:10.3109/08923979509016382

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractEffects 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 ofEscherichia coli, in vivoandin vitroproduction 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 ofE. coliafter 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-αserum levels after challenge with LPS were not modified by any of the triglycerides or their combinations. IL-6 increased by 43% with LCT-MCT mixture and by 39% with LCTs aloneversuscontrols. After a 3 hin vitrotreatment with LCTs, human monocytes were stimulated to release TNF-αat levels higher than those stimulated with the LCT-MCT mixture, and respect to controls. In contrast after 3 h the stimulation with LCT-MCT mixture induced a higher IL-6 release than controls and cells stimulated with LCTs alone, or with LPS.

ISSN:0892-3973    

DOI:10.3109/08923979509016383

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractThe 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 not always correlate with the percentage of NK-RP1+cells suggesting that capsaicin may interfere with maturation of lytic effector cells. Overall these results indicate a direct influence of the nervous system on natural immune cytotoxic functions.

ISSN:0892-3973    

DOI:10.3109/08923979509016384

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractAcebutolol induces transient polyclonal B cell activation in C57B1/6 mice but down-modulates the spontaneous polyclonal activation of NZBxNZW lupus mice. The immunomodulatory effects of this beta-blocker were studied in C57B1/6 mice injected with LPS or immunized with sheep red blood cells. The effect of acebutolol on the polyclonal activation of lymphocytes induced by LPS was also investigated in heterozygous and nu/nu C57B1/6 mice. Finally, the direct effet of acebutolol on spleen cells was studied in vitro. Acebutolol treatment for 15 days (50mg/kg/day) inhibited the polyclonal activation of lymphocytes induced by LPS in C57B1/6 and in C57B1/6 nu/nu mice, but increased the humoral response to sheep red blood cells in C57B1/6 mice. Moreover, spleen cells from C57B1/6 mice treated for 15 days with acebutolol showed an increased number of CD5+and CD4+lymphocytes, as well as an increased reactivity to concanavalin A but not to LPS. In vitro, acebutolol at 10−510−7M induced an increased reactivity of spleen cells from naive mice to concanavalin A, whereas it did not affect the B cell responsiveness to LPS. These results indicate that acebutolol modulates both T-cells and non T-cells in the immune system.

ISSN:0892-3973    

DOI:10.3109/08923979509016385

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractWe have investigated the effect of therapeutic doses of diazepam (7μg/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 thein vitroexperiments concentrations of 10−5M, 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 diazepamin vivoplays a role in both the nonspecific and specific immune response, producing in the macrophages a reorganization process of microfilaments.

ISSN:0892-3973    

DOI:10.3109/08923979509016386

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractStudies 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 at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significandy different from the single dose group. These 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.

ISSN:0892-3973    

DOI:10.3109/08923979509016387

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

AbstractToxic 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−1and 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.

ISSN:0892-3973    

DOI:10.3109/08923979509016388

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor