Showing papers in "Immunopharmacology and Immunotoxicology in 1993"
TL;DR: The data suggest that in vivo L-carnitine could prove useful in ameliorating both the immune response and lipid metabolism in patients with AIDS, irrespective of initial serum carnitines levels.
Abstract: Several reports indicate that systemic carnitine deficiency could occur in acquired immunodeficiency disease syndrome (AIDS), and that primary and secondary carnitine deficiency leads to critical metabolic dysfunctions.L-carnitine supplementation to peripheral blood mononuclear cells (PBMCs) of AIDS patients resulted in significant enhancement of the phytohemagglutinin (PHA)-driven proliferative response. High dose L-carnitine administration (6 gr per day for two weeks) to AIDS patients treated with zidovudine also led to increased PBMCs proliferation and reduced blood levels of triglycerides. In addition, a reduction of β2-microglobulin serum levels as well as circulating tumor necrosis factor (TNF)-α, mostly in patients exhibiting highly elevated levels, were found at the end of the treatment period.Our data suggest that in vivo L-carnitine could prove useful in ameliorating both the immune response and lipid metabolism in patients with AIDS, irrespective of initial serum carnitines levels. The ...
79 citations
TL;DR: The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in B-cell function indicates that this metal is immunotoxic at very low exposure levels.
Abstract: The major goal of the study was to determine the effects of high and low levels of mercury on human B-cells. Following treatment of B-cells with HgCI2 (0–1000 ng) and MeHgCI2 (0–100 ng), their activation
78 citations
TL;DR: Data indicate a significant contribution of the 1-naphthol leaving group to inhibition of T cell proliferation by carbaryl, and are consistent with inhibition of a serine hydrolase(s) as a mechanism contributing to the observed inhibition of IL2-dependent proliferation.
Abstract: The anticholinesterase (antiCHE) insecticides, a large family of pesticides used extensively throughout the world, inhibit serine hydrolases by carbamylating or phosphorylating a serine residue at the catalytic site. These insecticides are viewed as potential inhibitors of serine hydrolase-dependent immune functions including interleukin 2 (IL2) signalling. Previous studies in our laboratory have demonstrated that carbaryl (an antiCHE insecticide) produces a marked concentration-dependent inhibition of IL2 driven 1) proliferation of mouse CTLL2 cells, 2) proliferation of human natural killer (NK) cells, and 3) enhancement of target cell killing by human NK cells. In the present study, we examined the potential of 8 antiCHE insecticides (4 carbamates and 4 organophosphates) to inhibit IL2-dependent proliferation of mouse CTLL2 cells. The order of potency for T cell inhibition was carbaryl = dichlorvos > methiocarb > carbofuran > paraoxon > mevinphos > aldicarb = monocrotophos. In view of the relatively high inhibitory potency of carbaryl (a carbamate with low cholinergic toxicity), 3 metabolites and 5 congeners of carbaryl were tested for potency to inhibit CTLL2 proliferation. The data indicate a significant contribution of the 1-naphthol leaving group to inhibition of T cell proliferation by carbaryl, and are consistent with inhibition of a serine hydrolase(s) as a mechanism contributing to the observed inhibition of IL2-dependent proliferation.
64 citations
TL;DR: Responsibility to the immunotoxic effects of HgCl2 is, in part, dependent upon GSH levels and further that mercury inhibits GSH generation by lymphocytes and monocytes is clearly shown.
Abstract: The major goal of this investigation was to determine if the sensitivity of lymphocytes and monocytes to mercury (Hg++) was related to intracellular glutathione2 (GSH) levels and the thiol redox status [GSH/glutathione disulfide (GSSG)]. To isolate cells based upon their GSH content, T and B-cells were stained with monochlorobimane (MCB) and separated into high and low fluorescent groups by FACS analysis. Cells with high GSH fluorescence were found to be resistant to both the cytotoxic and immunotoxic effects of HgCl2 as evidenced by cell viability and their responsiveness to mitogen, respectively. In contrast, cells with low levels of GSH were extremely sensitive to mercury. To further examine the relationship between GSH level and mercury exposure, T-cells, B-cells and monocytes were treated with different doses of HgCl2 for 12 hrs. All cells exhibited a dose-dependent decrease in GSH content with a concomitant reduction in GSSG levels. However, the GSH/GSSG ratio in these cells remained constan...
41 citations
TL;DR: It is likely that TGF-beta protects against experimental auto-immune diseases by interfering with the entry of lymphoid cells into the target organs through inhibition of the upregulation of adhesion molecule expression on endothelial cells, and with subsequent inflammatory processes inside thetarget organs by antagonizing both the production and the effects of TNF.
Abstract: Injection of transforming growth factor $sZ1 (TGF-$sZ1) for five days during the late phase of the immunization process leading either to collagen type II induced arthritis (CIA) or to experimental allergic encephalomyelitis (EAE) protects against the development of these auto-immune diseases. Tumor necrosis factor a (TNF-$aL) injected during this same interval aggrevates CIA. In addition, anti-TGF-$sZ exacerbates and anti-TNF protects against CIA, acute and relapsing EAE, suggesting an important regulatory role for the endogenous production of the two cytokines on the severity of these diseases. More detailed studies about the mechanism of action of TGF-$sZ in acute EAE show that there is no detectable effect of TGF-$sZ on the development of sensitized T cells in vivo, as assayed by the proliferative responses of T cells from lymph nodes and peripheral blood to myelin antigens. Nevertheless, the number of lymphoid cells infiltrating the central nervous tissue is much greater in untreated than in ...
35 citations
TL;DR: The most susceptible stage of mitogen-triggered T and B lymphocyte proliferation was found to be at incipience, and Cytotoxicity could not be made responsible for drug effects.
Abstract: In vitro mitogen-driven lymphocyte proliferation tests (Con A, LPS) on murine lymph node and spleen cells revealed inhibition of T and B cell stimulation by different benzodiazepines and by PK 11195, with IC50 values in the low micromolar range. T cell responses as a consequence of recognition of alloantigens, as measured in mixed lymphocyte cultures (MLC), were affected in an analogous way. In all systems, agonists at peripheral type benzodiazepine receptors (Ro 5-4864 and the non-benzodiazepine compound PK 11195) and diazepam which acts on both, central and peripheral type benzodiazepine receptors, were most potent; clonazepam, a central type agonist, proved about half as active. The central type antagonist Ro 15-1788 failed to antagonize the action of diazepam and clonazepam. Variations among cells from several congenic strains of mice were modest. Cytotoxicity could not be made responsible for drug effects. The most susceptible stage of mitogen-triggered T and B lymphocyte proliferation was found to be at incipience. Radioresistant, adherent spleen cells, upon LPS-stimulation formed only small amounts of the cytokine IL-1. Its release was affected only at very high drug concentrations. Similar small amounts of IL-1 were generated during MLC; in this case, the drugs were about 10 times less potent than in mitogen-induced proliferation assays. Peripheral agonists were more active on IL-1 synthesis. Spleen cells stimulated with Con A and cultivated with the highest concentration of diazepam and clonazepam formed markedly greater amounts of IL-2 than those cultivated in medium, while at this concentration PK 11195 allowed no formation of the lymphokine.(ABSTRACT TRUNCATED AT 250 WORDS)
30 citations
TL;DR: Findings suggest a deficit in immune effector cell function after long term in vivo aluminum exposure, and demonstrate a shift in T-cell populations from treated mice with a deficiency of CD4+ cells.
Abstract: Swiss Webster mice were exposed to excess dietary aluminum (Al) (1000 μg Al/g diet, Al as Al lactate) from conception to 6 months of age. Splenic lymphocytes (106 per culture) were incubated for 24 hrs with concanavalin A (5 μg/ml). Concentrations of interleukin-2, interferon-γ and tumor necrosis factor-a, as measured in supernatants via ELISA with monoclonal antibodies, were depressed in spleen cells from aluminum treated mice relative to controls. Experiments using the flourescence activated cell sorter demonstrated a shift in T-cell populations from treated mice with a deficiency of CD4+ cells. These findings suggest a deficit in immune effector cell function after long term in vivo aluminum exposure.
28 citations
TL;DR: The coculture of peripheral blood mononuclear cells with various concentrations of ASTA-Z and IL-2 for 4 days produced significant suppression of cytotoxicity and lytic ability of the LAK cells against NK-sensitive and NK-resistant tumor cell lines.
Abstract: Recent studies combining chemotherapeutic agents with various biological response modifiers for the treatment of cancer have shown promising results. Cyclophosphamide (Cy) is the most widely used alkylating agent and a major constituent of combination chemotherapy regimens for many neoplastic diseases. It has been reported that Cy is a cytotoxic drug, which becomes immunosuppressive at higher doses. A synthetic metabolite of Cy, ASTA-Z, has recently been produced. ASTA-Z is more active and stable by itself and does not need to be metabolically converted to an active compound. the combined effect of Cy and interleukin-2 (IL-2) on the induction of lymphokine-activated killer (LAK) cells is not known. Therefore, we decided to investigate the effect of ASTA-Z on the induction and function of LAK. the coculture of peripheral blood mononuclear cells (PBMC) with various concentrations of ASTA-Z (0, 10−6 10−5, 10−4 and 10−3 dilution) and IL-2 (50 U/ml) for 4 days produced significant suppression of cytoto...
26 citations
TL;DR: Enhancement of in vivo polyclonal antibody production in peripheral blood lymphocytes from healthy subjects and cancer patients was elicited after the intravenous administration of 500 ml Ringer's acetate solution.
Abstract: The immunopharmacologic effects of Ringer's acetate on healthy persons and cancer patients were investigated. Enhancement of in vivo polyclonal antibody production in peripheral blood lymphocytes from healthy subjects and cancer patients was elicited after the intravenous administration of 500 ml Ringer's acetate solution. Allogeneic mixed lymphocyte reaction (MLR) and natural killer (NK) activity were also increased in the majority of healthy individuals and cancer patients when administered Ringer's acetate solution but not Ringer's lactate solution.
26 citations
TL;DR: CsA, CsC and metabolite M17 were the most active compounds upon the inhibition of lymphocyte proliferation induced by different mitogens and also on the proliferation of mixed lymphocyte cultures (MLC).
Abstract: Cyclosporine A (CsA) and its major metabolites: M1, M17 and M21 and two analogues: cyclosporines C (CsC) and D (CsD), were studied for their capacity to interfere with different in vitro activation pathways. Their inhibition potentials against the reaction of Graft-versus-Host (GvH) were also studied. The results showed: CsA, CsC and metabolite M17 were the most active compounds upon the inhibition of lymphocyte proliferation induced by different mitogens (ConA, PHA, PWM) and also on the proliferation of mixed lymphocyte cultures (MLC). The same results were observed concerning the direct activation by protein kinase C using a combined action of phorbol ester + calcium ionophore. In vivo using local GvH reaction, CsA and CsC proved more active than M17 in the two different combinations: H-2d --> (H-2b x H-2d)F1 and H-2k --> (H-2b x H-2k)F1 CsD and two metabolites M1 and M21 showed no or weak immunosuppressive effects. Overall, the immunosuppressive potency of six compounds could be schematized as: CsA > or = CsC > M17 > M1 > or = CsD > M21.
26 citations
TL;DR: Both serotonin and serotonin antagonists may inhibit mononuclear leucocyte migration, and no inhibiting effects of serotonin or the serotonin antagonists were found on the migration of polymorphonuclearLeucocytes.
Abstract: The effect of serotonin and the serotonin antagonists ketanserin, methiotepine and ICS-205-930 on the migration of leucocytes was studied by using the sealed capillary migration technique. The migration of mononuclear leucocytes was inhibited by serotonin at lO−4and 10−6-10−10mol/l. An inhibition of the mononuclear leucocyte migration was also caused by ICS-205-930 at 10 4mol/l, ketanserin at 10−4and 10−8-10−10mol/l and methiotepine at 10−4and 10−6-10−8mol/l. No inhibiting effects of serotonin or the serotonin antagonists were found on the migration of polymorphonuclear leucocytes. Thus, both serotonin and serotonin antagonists may inhibit mononuclear leucocyte migration.
TL;DR: RAPA proved highly effective in suppressing both the B lymphocytosis and the increase in circulating major histocompatibility complex class II+ cells observed following immunization, and a short course of RAPA following 1 degree immunization did no suppress 2 degree alloantibody responses elicited 6 weeks later.
Abstract: The immunosuppressive activity and comparative efficacy of rapamycin (RAPA), FK 506 and cyclosporine A (CsA) were investigated in rats following immunization with either xenogeneic sheep red blood cells (SRBC) or allogeneic blood transfusion. RAPA formulated in a polyethylene glycol vehicle, and at a dose of 1.5 mg.kg-1i. p., was relatively ineffective when compared with FK 506 (1 mg.kg-1) or CsA (15 mg.kg-1) in suppressing antibody production to SRBC. Like FK 506 and CsA however, RAPA proved highly effective in suppressing both the B lymphocytosis and the increase in circulating major histocompatibility complex class II+ cells observed following immunization. All three immunosuppressants caused thymic medullary atrophy, with evidence of epithelial cell damage and increased macrophage phagocytic activity. Administered i. m. (3 mg.kg-1 in olive oil), RAPA was also highly effective in suppressing 1 alloantibody responses to MHC class I antigens following blood transfusion. Unlike FK 506 and CsA howe...
TL;DR: It was shown that incubation in vitro of T cells with 5 mM of lithium chloride augmented interleukin-2 production, and it is believed that lithium increases the cytosol inositol triphosphate level and subsequently augmented impaired intracellular signal transduction in the T cells from patients with SLE.
Abstract: Cellular immunity is impaired in patients with systemic lupus erythematosus (SLE). A decreased production of interleukin-2 by T cells isolated from blood of patients with SLE was found. the decrease correlated with severity of the disease. It was shown that incubation in vitro of T cells with 5 mM of lithium chloride augmented interleukin-2 production. the increase in cultures of T cells from patients with SLE was higher that than in healthy individuals. It is belived that lithium increases the cytosol inositol triphosphate level and subsequently augmented impaired itra-cellular signal transduction in the T cells from patients with SLE.
TL;DR: It is indicated that subchronic exposure to low doses of mixture of styrene and dioctyl phthalate under certain conditions may modulate some of the immune functions as compared to exposure to either chemicals alone.
Abstract: Pathomorphological and immunological alterations caused by a mixture of styrene and dioctyl phthalate were studied in albino mice following oral administration of 0.02, 0.03, 0.05±LD50 of the mixture. The chemicals were mixed together proportionate to their respective LD50 values and fed in ground nut oil, 5d/wk for 4 weeks. Histological examination of spleen revealed considerable depletion of cellular population of lymphoid follicles which corresponded to the dose dependent decrease in splenic mononuclear cell population count. The thymic lobules revealed slight atrophy but accompanied by a significant increase in thymocyte population. Correspondingly few significant histological changes were observed in mesenteric and peripheral lymph nodes. The treatment caused impairment of primary humoral immune response to SRBC (IgM) but there was a significant increase in response of splenocytes to B-cell mitogen LPS. There was a suppression of cutaneous delayed type hypersensitivity and increase in splenic...
TL;DR: The initial cellularity depression and the following recovery was modified by both carboxymethyl derivatives of glucan, and cyclophosphamide treated mice exhibited less pronounced immunosuppression and more rapid hematopoietic recovery when administered with CMG.
Abstract: Carboxymethylglucan (CMG)1 in two different degrees of substitution of carboxymethyl groups (0.56 and 0.89) was administered to cyclophoshamide (CY) treated (200 mg/kg) C57B1/6 mice in three doses (10, 50, and 100 mg/kg) 24 h after CY. The influence of CMG administration on the cell suppression caused by CY was observed in the subsequent days. The cellularity of spleen, bone marrow and peripheral blood was quantified on days 2, 5, 8, 11, 15, and 21 after CY treatment.CY treated mice developed a significant decrease in peripheral blood cell counts, and spleen and bone marrow cellularity during the initial 5 days, followed by recovery in the next 15 days, with an overshoot reaction in spleen cellularity and erythrocyte levels.The initial cellularity depression and the following recovery was modified by both carboxymethyl derivatives of glucan. Cyclophosphamide treated mice exhibited less pronounced immunosuppression and more rapid hematopoietic recovery when administered with CMG, althought this rea...
TL;DR: RAPA's effects on kidney function were minimal at doses 50 times higher than its therapeutic dose established in the mouse, and RAPA exhibited a better therapeutic index than CsA in the mice.
Abstract: The effect of rapamycin (RAPA) on kidney function and histopathology was assessed in two strains of mice. Male C3H/HeJ mice were treated with RAPA for 4 days at doses of 25,50,75, and 100 mg/kg, ip and male C3H/HeJ or female Balb/cJ mice were both treated for 7 days at doses of 75,150 and 200 mg/kg. Cyclosporine (CsA) was also administered to female Balb/cJ mice at doses of 50, 100, 150 and 200 mg/kg, ip. RAPA-treated mice had elevated BUN levels but the effect was not dose-dependent and was not present in the high dose, 7-day study conducted in the C3H/HeJ mice. Body weights were significantly depressed in both of the 7 day studies but not in the 4 day study. Histopathologic examination of the kidneys revealed the presence of intracytoplasmic vacuolization in the proximal tubules in both of the 7 day studies at the higher dose only. There were no drug-related deaths. In die CsA-treated mice, multiple deaths were recorded in both the 150 mg/kg and 200 mg/kg dose groups, probably related to neuroto...
TL;DR: The administration of arecoline dosages 10 and 20 mg/kg bw daily for 4 days following SRBC immunization exerted dose-dependent suppression of primary antibody response, and the secondary HA and HL antibody titers were decreased.
Abstract: Arecoline, a major alkaloid of arecanut was examined to explore its modulatory influence on B cell-mediated immune response in a murine model system. The in vivo and in vitro effects were evaluated at sub-toxic concentrations of arecoline. The number of primary antibody forming cells (AFC) and hemagglutinating and hemolysis antibody titers to Sheep Red Blood Cells (SRBC) were evaluated in male mice. Arecoline exposure for a week invoked dose-dependent effect on primary antibody forming cells to SRBC with a maximum reduction at the dosage of 20 mg/kg bw, a moderate reduction at 10 mg/kg bw and no effect at 5 mg/kg bw dose level. HA and HL antibody titers to SRBC were suppressed markedly at arecoline dosage of 20 mg/kg bw and moderately at a dose of 10 mg/kg bw, given daily for 1, 2 or 3 weeks. The inhibitory effect of arecoline was not dependent on the duration of treatment. Like the primary antibody response, the secondary HA and HL antibody titers were also decreased after arecoline exposure. The...
TL;DR: Results indicate that alprazolam and triazolam, two triazolo-BDZ, do not modify in vitro phagocytosis and killing exerted by normal human polimorphonuclear cells and monocytes, and they significantly enhance T lymphocyte-dependent antibacterial activity in normal donors.
Abstract: Previous studies have demonstrated that benzodiazepines (BDZ) (e.g. diazepam) inhibit immune responsiveness. Since these drugs are largely used in psychiatric patients it is of great importance to verify the existence of different types of BDZ, which are not suppressive for the immune system. In this framework, our results indicate that alprazolam and triazolam, two triazolo-BDZ, do not modify in vitro phagocytosis and killing exerted by normal human polimorphonuclear cells and monocytes. On the contrary, they significantly enhance T lymphocyte-dependent antibacterial activity in normal donors. These data support the concept that triazolo-BDZ and, in particular, alprazolam may represent more appropriate drugs for the treatment of psychiatric patients (e.g. patients with phobic disorders and/or migraine) who display immunodeficits.
TL;DR: The beneficial role of thymostimulin is emphasized in RRI-affected children, suggesting a transient immaturity of the immune system as one of the possible pathogenetic factor.
Abstract: Recurrent respiratory infections (RRI) consist of more relapsing acute respiratory infections than the ones expected for the age [>6 acute respiratory tract infections (RTI) per year if age is >3 years, and >8 acute RTI per year if age is <3 years]. Concerning the pathogenesis of RRI, several investigations report the important role of environmental factors, early socialization and immunological dysfunctions, such as lymphocyte subpopulations alterations, IgG subclass deficiency and phagocytosis and/or opsonization deficit during acute infections. In this framework, we have studied the lymphocyte-dependent antibacterial activity (ABA) among 121 children affected by RRI. Results show a statistically significant alteration of this function in 38 children (31.4%): 19 of them exhibited an absent ABA (group 1), while in the others same function was reduced (group 2). A bovine thymic extract, thymostimulin, was administered to both groups by intramuscular injections (1mg/kg) for a 3 month cycle. At the ...
TL;DR: The results suggest that skin excision causes an inflammatory response in mice that results in an acute increase in the number of PMNs concomitant with the acute activation of hepatic MT synthesis.
Abstract: This experiment examined whether hepatic metallothionein (MT) synthesis induced by stressful stimuli could reinforce the peripheral leukocyte defense mechanism in mice. A 2 × 2 cm section of dorsal skin was excised from male ICR mice (7 w. o.), then the hepatic MT concentration and superoxide anion production (SOA) in peripheral leukocytes were measured at 6 and 24 hr after the excision. The 6 hr-hepatic MT level was 6 times greater in the skin-excised mice than in the controls. SOA in the skin-excised mice was 2.3 times greater at 6 hr than in the controls, then decreased to the control level by 24 hr. Food deprivation increased the hepatic MT and SOA levels at 24 and 48 hr to a remarkably greater level than in the controls. The increases in SOA, which was measured by chemiluminescence response (CD were found to be due to an increase in the number of polymorphonuclear leukocytes (PMNs) in the peripheral leukocytes in both the skin excision and food deprivation groups. These results suggest that s...
TL;DR: Naloxone, the opioid receptor antagonist, modulated the NK-cell activity like opioid peptides, i.e. resembled an opioid agonist, in an individual, donor dependent fashion.
Abstract: Naloxone at concentrations 10(-6) M to 10(-10) M modulated endogenous NK-activity in 11 of 14 samples of human peripheral blood lymphocytes after 18-hour incubation. The dose response usually showed two peaks, which varied with the donor. Enhancement was obtained in 6, suppression in 4, and both effects (depending on naloxone concentration) in 1 example; 3 donors were nonresponders. However, the overall effect of naloxone on endogenous NK activity was not statistically significant in the population as a whole. IL-2-stimulated NK-activity, was also altered by naloxone. The direction of the alteration depended on the degree of IL-2-induced NK-stimulation, and was donor-dependent. For example, naloxone enhanced NK-activity that had been stimulated by low IL-2 concentration (3 U/ml), but decreased NK-activity which had been stimulated by high (50 U/ml) IL-2 concentration. Naloxone 10(-7) M significantly reversed medium stimulation of NK activity, induced by 25 U/ml, in a group as a whole. Naloxone (10(-7) M to 10(-12) M) also modulated NK-activity stimulated by exogenous IFN alpha, as well as by endogenous, Poly-I.C-induced IFN. Decrease, or enhancement, depended on the degree of baseline NK-stimulation and varied with the donor. Short (2-hours) incubation with naloxone also resulted in the modulation of basal and IFN-stimulated NK-activity. Again, the effect varied with the donor and with the degree of lymphocyte activation. Thus, naloxone, the opioid receptor antagonist, modulated the NK-cell activity like opioid peptides, i.e. resembled an opioid agonist, in an individual, donor dependent fashion.
TL;DR: The data suggest that corticosterone induced a persistent decrease in total T cells, but only a transient effect on total lymphocyte subsets in the peripheral blood of Fischer 344 rats.
Abstract: This study was undertaken to determine the effects of continuous corticosterone administration on lymphocyte subsets in the peripheral blood of Fischer 344 rats. Pellets which released corticosterone over a 21 day period (0.07 mg/day, 0.48 mg/day and 4.8 mg/day) were implanted subcutaneously in male rats. Control rats received pellets containing only the excipient carrier. Rats in the test and control groups were sacrificed at 7, 14 and 21 days. Lymphocyte subsets were enumerated by dual color flow cytometry and the data expressed in absolute numbers/mm3. Effects were observed only in the animals treated with the highest dose which was 70,000 times the normal plasma level. the spleen, thymus and lymph nodes were examined for histopathological changes. At the seven day sacrifice there was a statistically significant decrease in total white blood cells and selective decrements in lymphocytes with reductions in the absolute numbers of the T helper/ amplifier, T cytotoxic/suppressor and B cells. Only ...
TL;DR: Alprazolam seems to be a more appropriate BDZ for treating immunocompromised patients, even including MWA patients, and results further support the existence of different classes of BDZ in terms of their immunomodulating capacities.
Abstract: Over the past few years, the immunomodulating role of benzodiazepines (BDZ) has been reported in literature. In particular, diazepam is an inhibitory BDZ with regard to its effects on the phagocytic and metabolic activities of polymorphonuclear cells (PMN) and monocytes, while triazolobenzodiazepines (alprazolam and triazolam) upregulate normal human peripheral blood T lymphocyte function. On these grounds, the administration of alprazolam (1 mg/per day for 1 month) in 13 patients with migraine without aura (MWA) and of lorazepam (2 mg/per day for 1 month) in 10 matched MWA subjects has been evaluated in terms of immune response. Results show that before administration of BDZ in both groups of patients phagocytosis and killing of PMN and monocytes were profoundly depressed and the same was true for the lymphocyte-dependent antibacterial activity. After one month treatment lorazepam further decreased lymphocyte function without modifying phagocytic capabilities. On the contrary, alprazolam increased PMN phagocytosis and killing and monocyte phagocytosis without modifying antibacterial activity values. Taken together, these results further support the existence of different classes of BDZ in terms of their immunomodulating capacities. Moreover, alprazolam seems to be a more appropriate BDZ for treating immunocompromised patients, even including MWA patients.
TL;DR: Novel lipopeptides 84/201 and 86/450 synthesized in this laboratory stimulated antibody and delayed type hypersensitivity (DTH) response to ovalbumin in guinea pigs and enhanced nonspecifically macrophage migration index (MMI), phagocytic activity and incorporation of [14C] glucosamine in peritoneal macrophages of the treated animals.
Abstract: Novel lipopeptides 84/201 and 86/450 synthesized in this laboratory stimulated antibody and delayed type hypersensitivity (DTH) response to ovalbumin in guinea pigs. Lipopeptide 86/450 also stimulated antibody and DTH responses in albino mice and enhanced nonspecifically macrophage migration index (MMI), phagocytic activity and incorporation of [14C] glucosamine in peritoneal macrophages of the treated animals. Proliferative response of splenocytes from lipopeptide 86/450 treated animals was significantly higher than that from untreated controls. Peritoneal macrophages from lipopeptide 86/450 treated mice were less susceptible to Leishmania donovani promastigote invasion when co-cultured in vitro. The treated animals on challenge with L. donovani promastigote/amastigote showed 80 to 90% lower intake of infection than the control animals.
TL;DR: Results showed that orally administered Shosaiko-to acts as a polyclonal B-cell activator which induces IgA production in the mucosal immune system.
Abstract: The Peyer's patches contain a large number of precursor cells committed to the production of immunoglobulin A (IgA) and play an important role in IgA response in the mucosal immune system. We investigated the induction of IgA producing cells in Peyer's patches by plaque forming cell assay after oral administration of a traditional Chinese herbal medicine, Xiao-chai-hu-tang (Japanese name: Shosaiko-to). The number of total IgA producing cells in the Peyer's patches detected by the protein-A plaque assay was increased about two-fold by Shosaiko-to administration and the numbers of both antiSRBC and anti-HRBC IgA producing cells were also increased by such a treatment. On the other hand, when SRBC alone were administered orally, only the number of anti-SRBC IgA producing cells was increased. Further, we examined T-cell subpopulations in the gut-associated lymphoid tissues after oral administration of Shosaiko-to by flowcytometry. Marked alternations in T cell subpopulations were not detected in the Peyer's patches, though TcR ys+T-cells in the
TL;DR: Under cyclosporine some 40% of patients may attain complete or partial remission of the nephrotic syndrome particularly if low-dose prednisone is associated, although relapse usually occurs when the drug is stopped.
Abstract: Idiopathic nephrotic syndrome encompasses two main forms of glomerular diseases, minimal change nephropathy and focal segmental glomerulosclerosis. Minimal change nephropathy is a disease of children which generally responds to corticosteroids. After remission, however, many patients show frequent relapses or steroid dependency. In these patients, cyclosporine may obtain remission of proteinuria in 80% of cases, although relapse usually occurs when the drug is stopped. Focal glomerulosclerosis is generally resistant to corticosteroids. Under cyclosporine some 40% of patients may attain complete or partial remission of the nephrotic syndrome particularly if low-dose prednisone is associated. Relapse of proteinuria usually occurs after stopping the drug. As cyclosporine may expose to chronic nephrotoxicity some guidelines should be followed to prevent this complication: - the doses should not exceed 5 mg/Kg/day - they should be adjusted whenever an increase in plasma creatinine of > or = 30% over the baseline values occurs - treatment should be stopped if there is no response within 3 months - a careful monitoring of patient under the supervision of a clinician trained with the use of cyclosporine is necessary. The term idiopathic nephrotic syndrome (INS) defines the association of a nephrotic syndrome with non specific glomerular lesions, in the absence of immune complex deposition (1). On the basis of renal histology two main types of INS are recognized: minimal change nephropathy (MCN) and focal and segmental glomerular sclerosis (FSGS).
TL;DR: It is suggested that guinea pig DTA reaction may provide a good screening way to find new sulfhydryl or disulfide compounds with low incidence of skin rash that have a good correlation with the frequency of the skin rashes referred to by the adverse effects in clinical reports of anti-rheumatic drugs.
Abstract: Delayed-type skin allergic (DTA) reactions induced by various sulfhydryl compounds were investigated. Sulfhydryl compounds investigated were bucillamine and D-penicillamine: antirheumatic agents, SA981: an intramolecular cyclic disulfide of bucillamine, tiopronin: a hepatoprotective and potent antirheumatic agent and captopril: antihypertensive and potent antirheumatic agent. Guinea pigs were sensitized on day 1 by subcutaneous injection and day 7 by subcutaneous and intramuscular injection of emulsions of these compounds (3 mg/animal) with Freund's complete adjuvant. Two weeks after the second sensitization, 0.3 mg/animal of each compound was intradermally challenged and the 24 hr DTA reaction was evaluated. A large number of sulfhydril compounds showed positive in the DTA reactions and the intensity of these reactions had a good correlation with the frequency of the skin rashes referred to by the adverse effects in clinical reports of anti-rheumatic drugs. It is suggested that guinea pig DTA reaction may provide a good screening way to find new sulfhydryl or disulfide compounds with low incidence of skin rash. A novel sulfhydryl compound N-(2,2-dimethyl-3-mercaptopropionyl)-L-cysteine (SA3441) and its intramolecular cyclic disulfide (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443), which show no DTA activity in guinea pigs, were found using the above-mentioned DTA reaction.
TL;DR: Findings show an impairment of calcium homeostasis in lymphocytes culminating into the biphasic immunomodulatory effects of γ-HCH.
Abstract: γ-HCH (Lindane) is reported to cause a biphasic immuno-modulation-stimulation followed by supression-after oral administration in mice (1). Role of calcium in this biphasic immuno-modulation. was. assessed after 4,12 and 24 wks of γ-HCH administration.45Ca-uptake was enhanced during the initial immuno-stimulation followed by decrease concomitant with immunosuppression. Lymphocyte proliferation was inhibited during both the phases of immune response by verapamil, a calcium channel blocker, and by trifluoperazine, a calmodulin inhibitor. These findings show an impairment of calcium homeostasis in lymphocytes culminating into the biphasic immunomodulatory effects of γ-HCH.
TL;DR: Norcantharidin can markedly inhibit lymphocyte proliferation stimulated by mitogen ConA or LPS in vitro, and the mixed lymphocyte reaction of mice, in a dose-related manner and has no effect on inactive lymphocytes that were cultured as control in medium without mitogens, suggesting that NCTD selectively acts on activated lymphocyte.
Abstract: Norcantharidin (NCTD) is a synthetic analog of cantharidin. It has potent antitumor properties without obvious side effect that Cantharidin has on urinary organs. It has been reported that NCTD is an immunological stimulator to NK, LAK, neutrophil and lymphocyte. In our experiment, however, we observed that NCTD can markedly inhibit lymphocyte proliferation stimulated by mitogen ConA or LPS in vitro, and the mixed lymphocyte reaction (MLR) of mice, in a dose-related manner. This occurred even when the drug was added 40 hours (for lymphocyte proliferation) or 72 hours (for MLR) after the cultures were initiated. On the other hand, NCTD has no effect on inactive lymphocytes that were cultured as control in medium without mitogens, suggesting that NCTD selectively acts on activated lymphocyte.
TL;DR: Monitoring fluorescence in cell suspensions and in single fura-2 loaded MOLT 4 lymphoblasts suggested that VIP modulates the amplitude of [Ca2+]i oscillations generated by a cytosolic [Ca1+] oscillator in a subset of cells at a concentration of 10(-12) M, a thousand-fold below the KD for the VIP receptor.
Abstract: Vasoactive intestinal polypeptide (VIP) has been shown to stimulate adenylate cyclase in a human lymphoblast cell line (MOLT 4). In the present study, we monitored fluorescence in cell suspensions and in single fura-2 loaded MOLT 4 lymphoblasts to determine if VIP modulates intracellular calcium concentrations ([Ca2+]i), and if this modulation is mediated by adenylate cyclase. The distribution of [Ca2+]i in resting and stimulated cells was non-homogeneous, with gradients of high [Ca2+]i present in the subplasmalemmal space. In a subset of cells (10-30% of all cells studied), [Ca2+]i showed La3+-sensitive, temporal changes in the form of [Ca2+]i oscillations with a baseline [Ca2+]i value of 115±10 nM, an oscillation amplitude of 150±18 nM and a mean period of 9.2±2s. The remaining non-oscillating cells showed a constant [Ca2+]i level of 75±5 nM (n=65 cells from 4 experiments). In the subset of cells with spontaneous [Ca2+]i oscillations, VIP dose-dependendy (10-12 to 10-8M) increased the amplitude ...