Showing papers in "Immunopharmacology and Immunotoxicology in 1994"

Suppression of B-cell mediated immunity in juvenile chinook salmon (Oncorhynchus tshawytscha) after exposure to either a polycyclic aromatic hydrocarbon or to polychlorinated biphenyls.

Abstract: Juvenile Chinook salmon (Oncorhynchus tshawytscha) were injected intraperitoneally with either the polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (DMBA)1 or with the commercial polychlorinated biphenyl (PCB) mixture, Aroclor 1254, to assess effects on the B-cell mediated immune response. B-cell mediated immunity was assessed by examination of the primary and secondary plaque-forming cell (PFC) responses of anterior kidney and splenic leukocytes to a T-independent antigen, trinitrophenyl-lipopolysaccharide (TNP-LPS) and to a T-dependent antigen, TNP-keyhole limpet hemocyanin (TNP-KLH). Salmon exposed to DMBA at dosages of 20% or 1% of the 96 hr LD50 (12.7 mg and 0.6 mg/kg of salmon, respectively) or to PCBs at a dosage of 20% of the 96 hr LD50 (54.0 mg/kg of salmon) exhibited a suppressed PFC response. The secondary PFC response of anterior kidney and splenic leukocytes to both antigens and the primary splenic PFC response to TNP-LPS were suppressed in salmon exposed to either DMBA...

Cytotoxic cells in immunodeficient athymic mice

Abstract: A studies of cytotoxic cells in athymic nude mice demonstrate higher cytotoxic activity of NK cells and macrophages than in their euthymic counterparts. The higher level of endogenous cytotoxic activity can be considered as complementary to the deficiency or lack of thymus dependent T lymphocytes and their functions. However, with increased age of mice some T lymphocytes and their functions can be demonstrated. By stimulation of splenocytes and lymph node cells in vitro with IL-2 or anti CD3 antibody cytotoxic activity towards P-815 (NK resistant, LAK sensitive) target cells can be generated. There exist data, which indicate that the cytotoxic activity is exerted by extrathymic pre-T lymphocytes with TcR gamma delta antigenic phenotype. The differences in transplantability of human tumors in athymic nude mice cannot be explained by defect in antigen recognition and in immune response of athymic nude mice, recipients of the xenografted material. The biological relevance in vivo of high endogenous cytotoxicity of NK cells observed in many strains of athymic nude mice remains obscure. The availability of new immunodeficient mouse models, e.g. scid mice deficient in B and T lymphocytes and with low level of NK cells, in which not only xenografted human tumor grow but human lymphoid cell can be transplanted as well, opens new and broader experimental possibilities, in which new preclinical immunotherapeutical approaches can be applied.

Comparison of immune functional parameters following in vitro exposure to natural and synthetic amphetamines.

Abstract: The potential of synthetic and natural amphetamines to modulate cellular immune effector and regulatory mechanisms was evaluated in an in vitro exposure system. Murine splenic lymphocytes and elicited peritoneal macrophages were cultured with 0.0001-100 μM of amphetamine sulfate, methamphetamine hydrochloride, or the (S) or (R) isomers of cathinone hydrochloride. T-lymphocyte regulatory function was assessed by quantitating the production of cytokines, and T-lymphocyte effector function was assessed by the induction of cytotoxic T-lymphocytes (CTL). B-lymphocyte function was measured by proliferation, and natural immunity was assessed by quantitating basal and IL-2 augmented natural killer (NK) cell activity. None of the compounds tested had any direct effect on cellular viability. Exposure to amphetamine resulted in a significant suppression of IL-2, but not IL-4, production by T-lymphocytes, as well as a suppression of B-lymphocyte proliferation only at the highest amphetamine concentration exam...

Effect of dietary vitamin E and selenium deficiency on chicken splenocyte proliferation and cell surface marker expression.

Abstract: Beginning at hatching, chicks were fed a Basal diet, without vitamin E or selenium (Se) or the same diet supplemented with vitamin E (100 IU/kg) and Se (0.2 ppm). The effect of these treatments on the expression of cell surface markers (CT-1a, CD3, CD4, CD8, sIgs, and Ia) defining specific thymocyte and peripheral blood leukocyte (PBL) subpopulations were examined using flow cytometric analyses. In parallel studies the effect of the dietary deficiencies on splenocyte proliferative responses to ConA or PHA stimulation was examined. The mean expression of CD3 and CT-1a per cell was increased while CD8 and CD4 expression was decreased on thymocytes from chicks fed the Basal diet. The proportion of double negative (CD4-, CD8-) thymocytes and single positive CD8+ thymocytes was significantly decreased while single positive CD4+ and double positive (CD4+, CD8+) thymocytes were significantly increased by the dietary vitamin E and Se deficiencies. The dietary deficiencies resulted in a decreased proportion of peripheral T cells and specifically decreased the number of CD4+ PBL. The proliferative response to both ConA and PHA was impaired by the vitamin E and Se dietary deficiencies. The proliferative response could be fully reconstituted but only after vitamin E and Se supplementation for periods longer than 1 week. Plasma SeGSHpx and alpha-tocopherol levels paralleled the mitogen responsiveness observed. These results support the conclusion that vitamin E and Se deficiencies may affect both the maturation of specific lymphocyte subpopulations and the functional and proliferative capabilities of the peripheral lymphocytes.

Augmentation of the resistance against Listeria monocytogenes by oral administration of a hot water extract of Chlorella vulgaris in mice.

Abstract: Oral administration of a hot water extract of Chlorella vulgaris(CVE)(20mg/mouse, 10 consecutive days) augmented the resistance against an i.p. infection with Listeria monocytogenes in mice. The numbers of bacteria in a CVE-administered group were significantly lower in the peritoneal cavity or spleen than those in a control group.FCM analysis revealed that γδ±Thy 1.2± cells in the nonadherent PEC from CVE-administered mice increased more prominently in number at the early stage on day 3 or on day 5 after infection as compared with those in control mice. The increment of γδ±Thy 1.2± T cells was also evident in spleen in CVE-administered mice at this stage after infection. The proportion of TCRαβ±Thy 1.2± T cells in the nonadherent PEC of a control group increased from 13% on day 0 to 49% at the late stage on day 10 after infection, whereas the proportion of TCRαβ±Thy 1.2± T cells in the nonadherent PEC in CVE-administered mice increased to 64% on this stage after infection in association with augm...

In vitro effects of cocaine, lidocaine and monoamine uptake inhibitors on lymphocyte proliferative responses.

Abstract: Cocaine was found to inhibit in vitro mitogen-stimulated rat B and T lymphocyte proliferation in a dose-dependent manner. The IC50 for B lymphocytes (70 μM) was 2 to 4 fold lower than that obtained with T lymphocytes. To determine whether ion channel blockade or inhibition of monoamine uptake produced a similar suppression of lymphocyte proliferation, the effects of pharmacological agents sharing each of these properties with cocaine were examined. Lidocaine (0.5 mM), a sodium channel blocker, had no significant effect on B and T cell proliferation. By comparison, cocaine inhibited lymphocyte responses by greater than 80 percent at this concentration. Monoamine uptake inhibitors were also found to suppress lymphocyte proliferation in a dose-dependent manner similar to that obtained with cocaine. Of those tested, desipramine and fluoxetine were considerably more potent than cocaine, nomifensine and nisoxetine. These data demonstrated the addition of cocaine directly to lymphocyte cultures resulted ...

Profile of Chicken Macrophage Functions After Exposure to Catecholamines In Vitro

Abstract: The effects of catecholamines (CA) on various chicken macrophage functions were examined. Macrophage monolayers were exposed to. 01,. 1,. 25, 1, 2, and 5 (μg/mL of dopamine (DA), norepinephrine (NE) and epinephrine (E) for 1 hr. All CA were toxic for macrophages at 1 -5 μg dose range resulting in 25-50% cell death. All CA at the. 1 and. 25 μg/mL level increased E. coli and sheep red blood cells (SRBC) phagocytosis by macrophages. the percentage of Fc-receptor positive macrophages increased after CA exposure. Prolonged exposure of macrophages (3 hr) reduced SRBC phagocytosis by DA-treated but not in NE-and E-treated macrophages. However, after 1 hr exposure and 3 hr recovery period, CA-induced changes were reversed in all but DA-treated cultures. Apomorphine and metoclopromide blocked DA whereas propranolol blocked NE and E effects suggesting specificity of the observed effects via catecholaminergic receptors on chicken macrophages. Dopamine and NE (.25 μg/mL) did not affect but E exposure enhanced...

Antibody to silicone and native macromolecules in women with silicone breast implants

Abstract: Silicone implants have been associated with the development of multiple organ system abnormalities, including rheumatic disorders, nervous system, pulmonary dysfunction associated with autoantibodies and abnormalities of cellular immunity. In this regards a number of case reports and series of articles have been described. We hypothesized that an immune reaction to silicone breast implants would include the host reactivity against silicone and the macromolecules within the microenvironment of the implant, and these autoantibodies may react with other tissue antigens far from the site of the implant. To test this hypothesis 520 Symptomatic women with Silicone Implants which have developed Silicone related Immunological disorders and have typically complained of breast pain, Myalgia-Arthralgia, fatigue, or generalized pain, were examined by their physician. Blood samples were obtained and examined for the presence of Silicone antibodies, Myelin Basic Protein and human serum albumin antibodies. These samples were then compared to 520 matched controls without implants. At least at the level of two standard deviation silicone specific antibodies, IgG, IgA IgM, IgE and IgG+IgA+IgM antibodies were detected above the mean of normal controls. When these antibodies were classified based on the specialty of the examining physician, the % of patients with Silicone Antibodies were varied; general practice 51.6, Rheumatology 58.7, and Plastic Surgery 83.3, which may relate to the severeness of the disease. Being that a large % of patients demonstrated very high levels of Myelin Basic Protein Antibodies, possible cross reactive antibodies were sought. However, absorption of highly positive sera for Silicone Antibodies with MBP did not change the levels of Silicone Antibodies. On the other hand, Silicone-HSA was able to reduce the antibody values significantly. This reduction in antibody levels by Silicone is the best indication for the specificity of these antibodies. Moreover when data for silicone antibodies and MBP antibodies was analyzed in patients some with high and others with medium or low levels of silicone antibodies, MBP antibodies did not correspond to the silicone antibody levels. Similarly human serum albumin antibodies which was significantly higher in patients with silicone implants did not correlate with levels of silicone antibodies. These results indicate that immune reaction to silicone and different tissue antigens do occur and they are initiated through different mechanisms. And since predominant antibody class against silicone, MBP and HSA was IgM, clonal activation of IgM is possible which certainly warrants further investigation.

Immunological consequences of in vitro exposure to lysergic acid diethylamide (LSD)

Abstract: The ability of lysergic acid diethylamide (LSD) to alter immune function after direct in vitro exposure was examined It was demonstrated that LSD is able to suppress the proliferation of B-lymphocytes; the production of the cytokines IL-2, IL-4, and IL-6; and the induction of cytotoxic T-lymphocytes at a concentration of 100 μM In vitro exposure to LSD had differential effects on natural killer (NK) cell activity, with significant enhancement of both basal and IL-2-augmented NK cell function at concentrations between 00001 and 01 μM, and suppression of NK response at 100 μM These results demonstrate that LSD may have a direct effect on components of the immune system at concentrations that may be reached upon human exposure

Augmentation of NK activity after oral administration of a traditional Chinese medicine, xiao-chai-hu-tang (shosaiko-to).

Abstract: We have shown that a traditional Chinese medicine, Xiao-chai-hu-tang (Japanese name: Shosaiko-to) augments natural killer (NK)1 activity in mice. The maximum augmentation of NK activity in the peripheral blood and liver was observed at 12 hr after administration of Shosaiko-to. NK activity was augmented by Shosaiko-to dose-dependently. The augmentation became significantly positive at a dose of 500 mg/kg, and the maximum effect was observed at a dose of 1000 mg/kg. The augmentation of NK activity appeared at first in the liver from 6 hr after administration of Shosaiko-to and became detectable later in the peripheral blood from 12 hr after the administration. Activation of NK cells by Shosaiko-to may occur in the liver and subsequently the activated NK cells may be supplied to the peripheral blood. Changes in percentages of cell surface markers (asialo GM1, CD3, CD4, CD8) after Shosaiko-to treatment were hardly detected, but augmentation of NK activity induced by Shosaiko-to was abrogated by anti-asialo GM1 antibody treatment before the cytotoxicity assay. In addition, cytotoxic activity to P-815 target cells was not detected in Shosaiko-to treated mice. Augmentation of NK activity by Shosaiko-to is probably mediated by functional activation of classical NK cells of asialo GM1+ phenotype. These results suggest that augmentation of NK activity in the liver is one of mechanisms involved in clinical efficacy of Shosaiko-to in patients with virus chronic hepatitis.

Adjuvant activity of the cell wall of bifidobacterium infantis for in vivo immune responses in mice

Abstract: We examined the adjuvant activity of the Bifidobacterial Cell Wall preparation (WPG) for in vivo immune responses in mice. We studied three classical immune responses, which are thought to be T-cell mediated responses, to evaluate the adjuvant activity of WPG. The delayed type hypersensitivity (DTH) responses of sheep blood red cell (SRBC)-sensitized mice were significantly augmented by WPG, although the enhancement varied with the timing, route and dosage of injection. The adjuvant activity of WPG was also confirmed by using a glutaraldehyde treated- and Concanavalin A associated- tumor vaccine (G-Con A tumor vaccine) system. BALB/c mice sensitized with G-Con A tumor vaccine and WPG improved synergistically in survival time and cure rate compared with those given G-Con A vaccine alone. Spleen cells of Meth A tumor-bearing mice induced antitumor neutralizing activity with the growth of tumor but the activity declined and disappeared at the late stage of tumor growth (over 28 days after tumor transplantation). On the other hand, antitumor neutralizing immunity was prolonged for as long as 33 days in mice inoculated with Meth A tumor and WPG. The requirement of a T-cell subpopulation in the spleen cells of tumor plus WPG treated mice was confirmed using anti-Thy 1.2 antiserum + complement to deplete them. The adjuvant activities of the Bifidobacterial cell wall demonstrated by the in vivo immune responses predict that Bifidobacteria may play a role as an immunomodulator in human and animal intestines.

Immunoglobulin levels and cellular immune function in lead exposed workers.

Abstract: The immunological status of lead acid batters workers with blood lead levels and urinary delta-aminolevulinic acid (ALA-U) concentrations ranging from safe to toxic levels has been examined and compared with those of non-exposed, age and sex matched controls. No differences in the serum concentrations of IgG, IgA and IgM between the populations were observed and there existed no correlation between blood lead level or ALA-U concentrations and serum immunoglobulin levels. In addition assessment was made of the capacity of peripheral blood mononuclear cells to respond to the mitogen phytohaemagglutin in (PHA), a correlate of T cell function. As before, there was no difference between exposed and control populations and no correlation between reactivity and blood lead concentration. Our data suggest that chronic exposure to lead fail to compromise lymphocyte function in man.

Inhibition of phytohaemagglutinin-induced lymphocyte proliferation by immunosuppressive drugs: use of whole blood culture.

Abstract: A whole blood lymphocyte proliferation assay was compared to a standard method requiring the isolation of lymphocytes from blood. Both methods were used to measure inhibition of proliferative responses of phytohaemagglutinin (PHA1)-stimulated human peripheral blood lymphocytes by tacrolimus (FK 506(1)), cyclosporine A (CsA1), rapamycin (RA1), dexamethasone (DEX1), prednisolone (PR1), and methylprednisolone (MP1). Three of the drugs studied (FK 506, CsA, and DEX) yielded similar IC50 values with both methods. The whole blood proliferation assay produced modestly lower IC50 values for RA, PR and MP. The whole blood lymphocyte proliferation method is simple and can be used when only limited volumes of blood can be obtained or isolation of cells gives unsatisfactory yields.

Downregulation of human polymorphonuclear cell activities exerted by microorganisms belonging to the alpha-2 subgroup of Proteobacteria (Afipia felis and Rochalimaea henselae).

Abstract: Intracellular pathogens have evolved effective mechanisms in order to survive in an intracellular environment, thus avoiding destruction by phagocytic cells. In this regard, a correlation between resistance to phagocytic killing and expression of pathogenic potency has been established. In this report, we have studied the interaction between human polymorphonuclear cells (PMN) and two gram-negative microorganisms, Afipia felis and Rochalimaea henselae, which belong to the alpha-2 subgroup of the class Proteobacteria. A. falis has been previously proposed as the causative agent of Cat Scratch Disease (CSD), but several recent lines of evidence attribute a major role to R. henselae. Of note, CSD is a syndrome characterized by a chronic lymphoadenopathy, involving macrophages and endothelial cells with a progression towards a granulomatous process and/or angiogenesis. Since members of the alpha-2 subgroup of Proteobacteria have the property to survive intracellularly, we have evaluated the effects exerted by A. felis and R. henselae on human PMN in terms of chemotaxis locomotion, degranulation and oxidative metabolism. Results will show an impairment of PMN activities as a consequence of the challenge with both microrganisms. In particular, inhibition of PMN oxidative function occurred either as result of a direct exposure to both A. felis and R. henselae or when PMN were primed by bacteria for the N-formyl-methionyl-leucyl-phenylalanine enhancement of the oxidative burst. These findings may account for the ability of A. felis and R. henselae to survive within PMN as expression of a further mechanism of pathogenic potency, influencing also the nature and the evolution of inflammatory response in the lesion sites.

Acrylamtoe Induced Immunosuppression in Rats and Its Modulan by 6-MFA, An Interferon Inducer

Abstract: In the present communication, we describe acrylamide (ACR) induced immunotoxicity and its modulation by an interferon inducer, the 6th mycelial fraction acetone (6-MFA) of Aspergillus ochraceus ATCC 28706. ACR administration to rats produced a significant decrease in the weight of spleen (p< 0.001), thymus (p< 0.001) and mesenteric lymph nodes (p<0.05). A decrease in cellularity of spleen (p< 0.001), thymus (p< 0.001), bone marrow (p< 0.001) and circulating blood lymphocyte population (p< 0.001) was also recorded. ACR suppressed the humoral as well as cell mediated immunity as assessed by erythrocyte antibody complement (EAC)-rosettes (p< 0.001), hemagglutination litre (p < 0.001), PFC (p < 0.001) and the delayed type hypersensitivity response against sheep red blood cells (SRBC, p< 0.001).ACR treated immunosuppressed rats when treated with 6-MFA restored the circulating lymphocyte number to the normal level and a partial recovery in the weight of spleen and thymus. Potentiation of EAC-rosettes, h...

The comparative pulmonary toxicity of beryllium metal and beryllium oxide in cynomolgus monkeys.

Abstract: Inhalation of beryllium (Be) may result in an immune-mediated, chronic granulomatous pulmonary disorder known as chronic beryllium disease (CBD). the physicochemical form of Be may affect the incidence and severity of CBD. We exposed cynomolgus monkeys, by bronchoscopic, intrabronchiolar instillation, to either beryllium oxide (BeO; heat-treated at 500°C) or Be metal at concentrations selected to achieve equimolar concentrations of available Be2+ ions dissolving from the particles. Monkeys underwent bronchoalveolar lavage of the right and left diaphragmatic lobes at 14, 30, 60, 90, and 120 days post exposure (dpe). Monkeys were sacrificed at 80 and 180 dpe for evaluation of histopathological pulmonary changes. Numbers of lymphocytes from lung lobes of Be metal-exposed, but not BeO-exposed, monkeys were increased at 14, 30 and 90 dpe. Lung lymphocytes were increased for BeO exposed monkeys only at 60 dpe. In vitro, Be-specific, lung lymphocyte proliferation occurred at 14, 60, and 90 dpe for lympho...

Induction of apoptosis in mouse thymocytes by cyclosporin A: an in vitro study.

Abstract: We investigated the in vivo effect of cyclosporin A (CsA) on mouse thymus and thymocytes. Administration of CsA (10 mg/kg of body weight) was found to induce a marked reduction in the size, weight and consistency of the thymus. These modifications were associated with thymic reticulo-epithelial cells (TREC) and thymocyte damage. Some of the damaged thymocytes displayed characteristic of cells undergoing apoptosis. Ultrastructural study of thymocytes and thymic tissue, as well as DNA electrophoresis of thymocytes, showed chromatin condensation, cellular shrinkage, and nuclear fragmentation in oligonucleosomal fragments. DNA labeling with propidium iodide (PI) of thymocytes from CsA treated mice cultured for 24 hrs showed an increased number of apoptotic nuclei. Furthermore, flow cytometric analysis using monoclonal antibodies (mAbs) specific for thymocyte subsets confirmed that CsA induces a large decrease in the relative number of mature single positive (SP) CD4+CD8- and CD8+CD4- thymocytes expressing high densities of CD3 and T cell receptor ab (TCR alpha beta) surface molecules, but also a decrease in the absolute number of the other thymocyte subsets. These results suggest that CsA causes macroscopic and ultrastructural modifications of the thymus, associated with an active process of cell death in mouse thymocytes in vivo. In line with these results we formulate a hypothesis concerning the stage of T-cell development at which CsA induces apoptosis.

Immunotherapy in chronic brucellosis. Effect of levamisole and interferon; mechanisms of action and clinical value.

Abstract: Thirty two anergic patients with chronic brucellosis treated with a)interferon-alpha2b(group 1), b)levamisole (group 2) and c)conventional therapy(group 3) were studied. the effect of treatment on T lymphocyte blast formation in the presence of PHA, specific cell mediated immunity against brucella antigens, titers of brucella antibodies and clinical symptoms were evaluated T lymphocyte blast formation was shown to range in normal levels in all patients before treatment compared to 10 normal controls suggesting against a generalized impairment of cell mediated immunity. Titers of brucella antibodies were significantly decreased in group 1, almost significantly in group 2 and were significantly increased in group 3 at the end of treatment. A significant improvement of symptoms as well as production of leukocyte migration inhibition against brucella antigens were noted in both groups 1 and 2, in contrast to group 3. This response to treatment was however greater in group 1. These findings demonstrate...

The induction of cytokine gene expression in murine peritoneal macrophages by Pseudostellaria heterophylla.

Abstract: We have previously shown that a mitogenic fraction (PH-I) separated from Pseudostellaria heterophylla (P. heterophylla) could act as a priming agent for the release of tumor necrosis factor-α (TNF-α) in mice. In the present study, PH-I was further purified by gel filtration chromatography and the resulting three fractions (PH-I A, PH-I B and PH-I C) were assessed for the induction of TNF-α, interleukin-1-α (IL-1-α) and IL-1-s gene expression in mice by enzyme-linked immunosorbent assay and polymerase chain reaction. It was found that fraction PH-I C from P. heterophylla was the most potent priming fraction among the three fractions for the induction of TNF-α in serum and the TNF-α mRNA in murine macrophages. Moreover, all three fractions were found to increase the expression of IL-1-α mRNA while PH-I C showed the most potent activating effect on the expression of IL-1-s mRNA.

Corticotropin-Releasing Factor Reduces Lipopolysaccharide-Induced Pulmonary Vascular Leak

Abstract: Previous studies have suggested that corticotropin-releasing factor (CRF) has immunoregulatory effects in addition to its neuroendocrine role. We examined the ability of CRF to inhibit lipopolysaccharide (LPS)-induced pulmonary vascular leak in vivo. Female BALB/C mice were treated with either normal saline (NS) or CRF prior to injection with LPS. Pulmonary vascular leak was inhibited by CRF as assessed by measurement of lung wet-to-dry ratios. The stress-induced increase in serum corticosterone levels in mice injected with LPS alone was not further increased by treatment with CRF. This indicates that the effect of CRF was not mediated centrally by stimulation of endogenous steroid release. Histologic examination of the lungs revealed that leukocyte infiltration was significantly depressed in CRF-treated mice thus confirming the protective effect of CRF. In addition, a modest prolongation of survival was demonstrated in CRF-treated mice following challenge with LPS (p=.08). These data indicate the...

Levamisole as an immunopotentiator for T cell deficiency.

Abstract: Levamisole, a widely used antihelminthic drug has been shown to restore cutaneous delayed hypersensitivity in anergic patients with cancer and to amplify the activation of T lymphocytes by in vitro mitogens. Levamisole has been approved for the treatment of colon cancer in combination with 5 Fluorouracil. Herein we report a case of a 5 1/2 y.o. male who presented with a fulminant, disseminated mycobacterial infection of his joints secondary to a deficiency in his cellular mediated immunity in association with chemotherapy for a T cell leukemia. The patient was treated with Levamisole resulting in restoration of his T cell functions and resolution of his mycobacterial infection.

Immunomodulating effect of met-enkephalin on different stages of lymphocyte proliferation induced with concanavalin A in vitro.

Abstract: Met-enkephalin (ME) in the range of concentrations 10−15 M to 10−9 M has exhibited an immunomodulating effect on concanavalin A (Con A) induced proliferation of mice lymphocytes from lymph nodes in vitro. The effect of ME was shown to vary with the stage of lymphocyte activation and to depend on the mitogen dose. In the case that ME and Con A were injected simultaneously, at the zero time of proliferation, maximum inhibition was observed on the first and fourth days. In an other set of experiments when ME was added at intervals of 4 hours before measuring the proliferation response value, both inhibition (after 24 hours of proliferation) and stimulation (after 28 and 96 hours) were observed. Opioid ligands of various classes were found to act in the same manner as ME. Naloxone was shown to block the immunomodulating effect of opioids.

Dibutyltin dilaurate induced thymic atrophy and modulation of phosphoinositide pathway of cell signalling in thymocytes of rats.

Abstract: A marked dose dependent reduction in thymus weight and its nucleated cell counts with histological alterations was observed in rats exposed to oral dibutyltin dilaurate (DBTL) for 2 weeks at 2, 4, 8 or 16 mg/kg body weight. The incorporation of [3H]-inositol into all the three major phosphoinositides was drastically reduced in thymocytes in a dose dependent manner. Furthermore, the basal and the mitogen (Con A) stimulated [3H]-inositol phosphates generation was diminished significantly in 8 mg DBTL group. However, in vitro incubation of DBTL with thymocytes failed to evoke any change in phosphoinositide hydrolysis. Similarly, a time and dose dependent inhibition in phosphoinositide synthesis with as high as 80% by 10 microM DBTL was exhibited under in vitro conditions. A 130% and 600% enhancement of protein kinase C (PKC) activity in thymocytes was seen in 4 mg and 8 mg DBTL group, respectively. Addition of DBTL to the cell free assay system of thymocytes resulted in a concentration dependent activation of the enzyme activity. A dose dependent increase in intracellular calcium was also evident when DBTL was added to thymocytes under in vitro conditions. These results are of significance and may bear close relationship to the observed thymic atrophy by DBTL.

Comparative Study of Immunomodulatory Properties of Muramyl Peptides On Immune System Cells of Yg and Old Mice

Abstract: The immunomodulatory effects of two synthetic muramyl peptides (MP): muramyl dipeptide and glucosaminyl- muramyl dipeptide have been compared. It was shown, that MP effects on immune response are a consequence of the alteration in T lymphocyte regulators balance. MP action on old mice immune response and lymphocyte function was stimulating only: increasing of T helper precursors frequency and IL-1 production by macrophages. In the latter both MPs acted as correctors, recovering the decreased IL-1 production by old mice macrophages to young control level.

In vivo effect of omeprazole on hla-dr expression and the nonocyte-macrophage function in patients with duodenal ulcer disease

Abstract: It is not known if onieprazole possesses any action on immune system. Therefore, we examined the effect of oineprazole on parameters of cellular immunity [T-cell subsets-CD3±, CD4±, CD8± - and HLA-DR expression on peripheral blood lyniphocytes (PBLs)] and on function of peripheral blood monocyte-macrophages (PBMMs) [random migration (RM), directed migration (DM), phagocytosis index (P-I) and HLA-DR expression] in 13 duodenal ulcer patients before and during 3-mo omeprazole treatment. The number of T-cell subsets varied at pretreatment values (p>0.05), whereas the percentage of HLA-DR positive PBLs increased significantly after 3-mo therapy (p< 0.001). On the other hand, all studied parameters concerning PBMMs (RM, DM, P-I and HLA-DR expression) increased significantly after 3-mo therapy (p<0.001, p<0.001, p<0.003, p<0.001, respectively vs. baseline values).In conclusion, oineprazole exerts an immunopotentiating effect on functions of PBMMs and may also influence T-cell function. These effects can ...

Thalidomide does not perturb cd2, cd4, cd5, cd8, hla-dr, or hla-a, b, c molecules in vitro on the membranes of cells with immune potential

Abstract: Thalidomide dramatically relieves the signs and symptoms of erythema nodosum leprosum (ENL). ENL is an acute inflammatory complication of lepromatous leprosy. the cause(s) of ENL as well as the mechanism of action of thalidomide in arresting ENL are unknowns.It has been suggested that ENL is the consequence of a transient activation of a cell-mediated-immune (CMI) response to Mycobacterium leprae. to initiate a CMI response, an interaction between adhesion and/or signal transducing molecules on T-cells and molecules on antigen presenting cells would occur. An alteration, induced by thalidomide, of one or more of the molecules on T-cells or antigen presenting cells that are essential to maintaining the reactive state of ENL, could explain Thalidomide's ability to attenuate ENL.Thalidomide did not modify: (a) adhesion and/or signal transducing molecules such as CD2, CD4, CD5 and CD8, or (b) molecules that facilitate antigen presentation such as HLA-DR, HLA-A, HLA-B, or HLA-C.

Changes in the frequency of splenic immunocompetent cells in rats exposed to carbon monoxide during gestation

Abstract: The aim of the present study was to evaluate whether prenatal exposure to relatively low concentrations of carbon monoxide (CO) may alter the frequency of splenic cells either in young (15—21 days) or in aged rats (18 months). Wistar female rats were exposed to 75 and 150 ppm of CO from day 0 to day 20 of pregnancy, respectively.The results show that prenatal exposure to 150 ppm of CO significantly decreases the number of leucocyte common antigen (LCA±) cells in 21 day old male rats, whereas other cellular populations, such as macrophages, Major Histocompatibility (MHC) II cells, T and B lymphocytes display only a trend towards a reduction without achieving statistical significance. The alterations in LCA± cell frequency produced by gestational exposure to CO were reversible.These data further extend previous findings showing that rats prenatally exposed to moderate concentrations of CO exhibit subtle immunological changes in the absence of overt signs of toxicity.

Modulation of amphotericin B activity by association with mannose ester

Abstract: The biological and molecular properties of a new formulation of Amphotericin B complexed with the surfactant paImitoyl mannose were studied in in vitro as well as in in vivo situations. The properties analyzed include toxicity towards two types of mammalian cells and four fungi strains, effect on macrophage activity, inflammatory properties, acute toxicity in mice and spectral behavior in presence of foetal calf serum or 6% propanol. The results demonstrate that, in presence of palmitoyl mannose, the cytotoxicity of AmB is decreased towards both, fungal and mammalian cells while its fungistatic potential is increased, its inflammatory properties are conserved and its acute toxicity is significantly diminished. These effects can be potentially explained by the formation of a complex between AmB and the sugar ester that impedes the interaction of the drug with either serum components or cell membrane constituents. The overall properties of AmB in the complex would be expected to favor an increase in...

Effects of Pseudostellaria heterophylla on proliferation and differentiation of murine bone marrow cells.

Abstract: The incorporation of tritiated thymidine into the DNA of murine bone marrow cells could be stimulated by fraction PH-I Ba separated from the roots of Pseudostellaria heterophylla in a dose-dependent manner in vitro Moreover, PH-I Ba could induce the differentiation of murine bone marrow cells from pluripotent haemopoietic stem cells into macrophages-like cells in vitro Autocrine or paracrine stimulation of granulocyte-macrophage colony stimulating factor was likely to underly the induction of differentiation Therefore, PH-I Ba was proved to be an immunostimulating agent for mouse marrow hematopoiesis and was found to be a polysaccharide The sugar components were analyzed by Gas Liquid Chromatography of their alditol acetates

The interaction of immunosuppressive compounds in tandem stimulated peripheral human lymphocytes

Abstract: We have developed an in vitro system to model the interactions of drugs used to treat transplant rejection. This system consists of stimulation of human lymphocytes with a primary mitogen (anti-T-cell receptor complex antibodies (OKT3 or wt31)) and treatment with a primary immunosuppressive drug (ISD) (Cyclosporine A (CsA) or FK-506)). This is later followed by stimulation with a secondary mitogen (Interleukin-2 or anti-CD28), and treatment with a second ISD. This system allows a variety of concentrations and compounds to be rapidly tested. We have used this system to study the effect of various compounds when used as either primary or secondary ISDs. Our results show that when CsA is used as the primary ISD, further proliferation can be inhibited by rapamycin, mycophenolic acid, or suramin. When FK-506 is the primary ISD, inhibition of proliferation by rapamycin is variable depending on the primary and secondary mitogens. If rapamycin is the primary ISD, both CsA and FK-506 show antagonistic interactions. These results suggest that the order in which combinations of ISDs are administered in transplantation may have significant effects on the clinical outcome.