Showing papers in "Immunopharmacology and Immunotoxicology in 1998"
TL;DR: Results suggest that a different cytokine pattern could be probably involved in the pathogenesis of relapsing-remitting MS.
Abstract: Levels of tumor necrosis factor (TNF)-α, granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-10 and transforming growth factor (TGF)-β in cerebrospinal fluid (CSF) and serum of 29 patients with multiple sclerosis (MS) of the relapsing-remitting type and of 20 controls with other non inflammatory neurological diseases were studied. Sixteen patients were in the active phase of disease and 13 in remission. In CSF, higher IL-10 and TGF-β concentrations were found in patients with a stable phase of MS, while in the active phase there were elevated levels of TNF-α and GM-CSF. These results suggest that a different cytokine pattern could be probably involved in the pathogenesis of relapsing-remitting MS.
150 citations
TL;DR: It is indicated that DEP can enhance airway responsiveness associated with allergen exposure, and experimental evidence thatDEP may deteriorate the pathophysiology of allergenic-related respiratory disease such as allergic asthma is provided.
Abstract: We have previously reported that intratracheal instillation of diesel exhaust particles (DEP) enhances allergen-induced eosinophilic airway inflammation, local expression of interleukin-5 and granulocyte macrophage-colony stimulating factor, and allergen-specific production of IgE and IgG in mice. The present study was undertaken to elucidate the effects of DEP on airway hyperresponsiveness as another characteristic feature of allergic asthma. The animals were randomized into four experimental groups that received intratracheal instillation with vehicle, ovalbumin (OVA), DEP, or the combination of OVA and DEP on a weekly basis for 6 weeks. Respiratory resistance (Rrs) was measured 24 h after the last instillation. An increase in Rrs in animals that inhaled acetylcholine was significantly greater in the combined treatment with OVA and DEP than in the other treatments. The present study indicates that DEP can enhance airway responsiveness associated with allergen exposure, and provides experimental ...
82 citations
TL;DR: It is shown that 1 mM sulfide is able to enhance the apoptotic fate of human granulocytes by increasing: i) the number of cells containing pyknotic nuclei, ii) the internucleosomal cleavage, and, iii) the intensity of tubulin immunofluorescence staining.
Abstract: Hydrogen sulfide is a toxic metabolite released by several bacterial agents under anaerobic conditions. In the present paper, we investigated the effects of sulfide on polymorphonuclear cell (PMN) apoptosis, a mechanism suggested for limiting the toxic potential of neutrophils in inflammatory sites. We showed that 1 mM sulfide (concentration not conditioning PMN viability) is able to enhance the apoptotic fate of human granulocytes by increasing: i) the number of cells containing pyknotic nuclei, ii) the internucleosomal cleavage, and, iii) the intensity of tubulin immunofluorescence staining. The sulfide effect is partially prevented by ionomycin and this finding is consistent with the hypothesis of the inhibiting role played by high levels of cytosolic calcium in PMN apoptosis modulating.
71 citations
TL;DR: It is suggested that prolonged administration of low doses of E2 and T but not DHT to chicken may induce immunosuppressant effect.
Abstract: Administration of either 1 μg kg-1 BW oestradiol 17β (E2), 0.1 mg kg-1 BW testosterone (T) or 0.2 mg kg-1 BW dihydrotestosterone (DHT) in feed to broiler chicks for 50 days caused increased serum concentration of the hormones compared to the control birds that were given no drugs. E2 and T but not DHT resulted in a significant decrease of the total number of leukocytes, lymphocytes and the weight of bursa of Fabricious. The hormones significantly reduced the macrophage phagocytic activity compared to controls. It is suggested that prolonged administration of low doses of E2 and T but not DHT to chicken may induce immunosuppressant effect.
54 citations
TL;DR: It is suggested that chemotherapeutic paclitaxel regimens impart significant but reversible inhibition of lymphocyte populations, and IL-12 may be a useful ancillary immunotherapeuter to overcome pac litaxel-induced modulation of lymphocytes activities.
Abstract: The antineoplastic agent paclitaxel (TAXOL®) is a potent inhibitor of tumor cell division and a useful chemotherapeutic for the treatment of refractory ovarian and breast carcinoma. Multiple immune system actions have been ascribed to paclitaxel, including the capacity to induce macrophage antitumor cytotoxic molecule production. However, T-cells are susceptible to paclitaxel's cytostatic functions, and no studies have investigated the effects of direct paclitaxel administration on lymphocyte function in the tumor-bearing host (TBH). Because paclitaxel is currently used as an antitumor chemotherapeutic agent and tumor growth alters leukocyte functions, we assessed T-cell function following chemotherapeutic-type paclitaxel treatment. Paclitaxel administration significantly compromised the proliferative capacity of both normal host and TBH lymphocytes in vitro. Although tumor growth impaired T-cell interferon-y (IFN-y) production, paclitaxel treatment did not alter IFN-γ. We speculate that the immun...
44 citations
TL;DR: It is found that there is no correlation between immune function and development of preneoplastic colon lesions in rats fed QUE, and in vitro exposure of splenic natural killer cells to 1mM QUE significantly decreased natural killer cell cytotoxicity.
Abstract: Rats fed 100 mg/kg quercetin (QUE) daily for 7 weeks had significantly enhanced natural killer cell activity compared to their vehicle (VEH)-fed control. In contrast, rats fed 100 mg/kg QUE and treated with the colon carcinogen, azoxymethane had significantly reduced natural killer cell activity compared to their VEH-fed azoxymethane-treated control. There was no significant difference in natural killer cell activity between the two control groups. Antibody production and delayed-type hypersensitivity were not altered by QUE feeding in any treatment group. In vitro exposure of splenic natural killer cells to 1mM QUE significantly decreased natural killer cell cytotoxicity. Lower QUE concentrations produced a non-significant reduction in natural killer cell activity that was restored to control values at 1 x 10(-13)M QUE. The distribution, multiplicity and total number of colonic preneoplastic lesions, aberrant crypt foci, was not significantly different in the QUE-fed azoxymethane-treated rats when compared to azoxymethane-treated vehicle-fed rats at the conclusion of 7 week feeding period. We found no correlation between immune function and development of preneoplastic colon lesions in this study.
35 citations
TL;DR: This review will place emphasis on some clinical conditions, such as phobia and migraine without aura (MWA), characterized by anxiety disorders, where the presence of central and/or peripheral BDZ receptors on immune cells seems to be the key mechanism responsible for the immunomodulation exerted by these drugs.
Abstract: Psychoneuroimmunology is a growing scientific field which deals with the mutual interplay between nervous and immune systems. In this framework, many data have demonstrated that cytokines (CKs) derived from the periphery are able to cross the blood brain barrier and act upon the central nervous system (CNS) [e.g., the hypothalamic-pituitary-adrenal axis (HPAA)], thus regulating several physiological functions (thermoregulation, sleep, appetite) or damaging the nervous tissue, when released in exaggerated amounts. On the other hand, nervous cells, such as astrocytes and microglial cells also generate proinflammatory CKs which may be detrimental for the CNS. The neuromodulating CK network can be triggered by microorganisms and/or their products (i.e. bacterial endotoxins), but also stressful life events may activate the HPAA, thus affecting the immune system function. This review will place emphasis on some clinical conditions, such as phobia and migraine without aura (MWA), characterized by anxiety disorders. Patients affected by these neuropsychiatric alterations exhibit multiple functional deficits of phagocytes and T lymphocytes which allow penetration of various pathogens into the host. This is also supported by the detection of circulating bacterial endotoxins and the evidence of both spontaneous and induced exaggerated release of proinflammatory CKs in phobic and MWA patients. The possible iatrogenic effects of benzodiazepines (BDZ) on the immune system have been evaluated by in vitro and in vivo studies. In this respect, it emerges that diazepam exerts an inhibitory function on the immune system, while alprazolam behaves as an immunoenhancer. The presence of central and/or peripheral BDZ receptors on immune cells seems to be the key mechanism responsible for the immunomodulation exerted by these drugs.
34 citations
TL;DR: Treatment with ML-I and IL-2 might provide an approach to induce maximum cytotoxicity against tumors and to recruit both T and NK cells for tumor therapy.
Abstract: This report demonstrates that in vitro activation of human cells with the beta-galactoside-specific lectin from mistletoe (ML-I) or interleukin-2 (IL-2) results in different patterns of activation and function of cytotoxic cells. It is now well established that natural killer (NK) and lymphokine-activated killer (LAK) cytotoxicity is mainly mediated by resting (NK) and IL-2-activated (LAK) CD56-positive (+) cells respectively. Culture of peripheral blood lymphocytes (PBL) for 3 days with ML-I led to expansion and activation of T cells which demonstrated NK- and LAK-like cytotoxicity. T lymphocyte subset analysis revealed that in total PBL, ML-I preferentially stimulated and expanded CD8+ T cells which mediated the cytotoxic effect. Incubation of highly purified CD8+ T cells alone with ML-I did not lead to induction of cytotoxicity, which required the presence of both CD4+ and CD14+ (monocytes) cells, suggesting that ML-I does not exert a direct effect on CD8+ T cells. Activation of PBL with both ML-I and IL-2 resulted in simultaneous induction of T and CD56+ cell-mediated NK and LAK cytotoxicity. These data suggest that treatment with ML-I and IL-2 might provide an approach to induce maximum cytotoxicity against tumors and to recruit both T and NK cells for tumor therapy.
33 citations
TL;DR: The authors report their clinical experience with VRCTC-310 in two patients suffering with advanced cancer in which the skin was severely compromised and demonstrated not only an objective complete response of the primary tumor mass, but the disappearance of supraclavicular tumor mass as well a significant reduction in lymphangitis.
Abstract: The authors report their clinical experience with VRCTC-310 in two patients suffering with advanced cancer in which the skin was severely compromised. VRCTC-310 is a combination of the snake venoms crotoxin (CT) and cardiotoxin (CD). The local (peritumoral) treatment with the drug (0.O14 mg/kg/week during 6 weeks) provoked the complete disappearance of a relapsed skin squamous cell cancer in one patient. The other patient was an aged woman with local-advanced breast cancer (carcinoma en cuirasse) who was inoculated intra-and-peritumoral with VRCTC-310. After 6 weekly courses (0.014 mg/kg/week) with the drug a > 80% tumor reduction was seen. A 133 days follow-up demonstrated not only an objective complete response of the primary tumor mass, but the disappearance of supraclavicular tumor mass as well a significant reduction in lymphangitis. To our knowledge, this is the first communication about the in vivo antitumoral activity of VRCTC-310 when injected locally to humans. Further studies are now in progress.
32 citations
TL;DR: Evidence that sCD14 and interferon (IFN)-gamma serum levels are significantly higher in chronic hepatitis C (CH-C) patients than those detected in normal donors is provided and a putative pathogenetic role for sCD 14 LPS-LBP complex in subjects affected by CH-C virus infection is suggested.
Abstract: CD14 is a monocyte/polymorphonuclear cell receptor for lipopolysaccharide (LPS)-LPS Binding Protein (LBP), which mediates most of the toxic effects exerted by such a bacterial component in the host. Here, we provide evidence that sCD14 and interferon (IFN)-γ serum levels are significantly higher in chronic hepatitis C (CH-C) patients than those detected in normal donors. On the other hand, CD4+/CD8+ antibacterial activity is depressed, thus facilitating entry of bacteria into the host.Of note, all these immune parameters are not modified by in vivo IFN-α administration over a period of one year. Finally, after 12 months of IFN-α treatment number of CH-C patients with detectable levels of plasmatic LPS increased, thus indicating a continuous release of LPS into the host and also suggesting a putative pathogenetic role for sCD14 LPS-LBP complex in subjects affected by CH-C virus infection.
31 citations
TL;DR: Oral administration of SST shows anti-influenza virus activity in the nasal cavity by activation of T-cell in Peyer's patch lymphocyte and stimulation of production of anti- inf fluenza virus IgA antibody in nasal lymphocyte.
Abstract: When BALB/c mice were treated with a Kampo (Japanese herbal) medicine "Sho-seiryu-to (SST)" (1 g/kg, 10 times) orally from 7 days before to 5 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34 by nasal-site restricted infection, SST caused increment of the influenza virus hemagglutinin-specific IgA antibody secreting cells in nasal lymphocyte but not in Peyer's patch lymphocyte at 6 days after infection in comparison with water-treated mice. Oral administration of SST also augmented IL-2 receptor beta chain+ (activated) T-cell in Peyer's patch lymphocyte, but not in the nasal lymphocyte. We previously reported that SST showed potent anti-influenza virus activity through augmentation of the antiviral IgA antibody titer in the nasal and broncho-alveolar cavities of the mice (T. Nagai and H. Yamada, 1994, Int. J. Immunopharmacol. 16, 605-613). These results suggest that oral administration of SST shows anti-influenza virus activity in the nasal cavity by activation of T-cell in Peyer's patch lymphocyte and stimulation of production of anti-influenza virus IgA antibody in nasal lymphocyte. When ovalbumin-sensitized allergic pulmonary inflammation model mice were administered orally with SST (1 g/kg) from 8 days before (11 times) or from 2 h after (4 times) to 4 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34, replications of the virus in the both nasal and broncho-alveolar cavities or only nasal cavity were significantly inhibited at 5 days after infection in comparison with water-treated control by augmenting antiviral IgA antibody, respectively. These results suggest that SST is useful for both prophylaxis and treatment of influenza virus infection on patients with allergic pulmonary inflammation, such as bronchial asthma.
TL;DR: The capacity of Taraxacum officinale (Compositae) (TOAE) to restore NO production from interferon-gamma (IFN-Gamma)-primed mouse peritoneal macrophages is the result of TOAE-induced TNF-alpha secretion.
Abstract: Nitric oxide (NO) produced at high concentrations by the inducible NO synthase is an important effector molecule involved in immune regulation and defense. The involvement of NO in the toxicity of cadmium (Cd) has been proposed. We have established that Cd inhibits the production of NO by recombinant IFN-gamma (rIFN-gamma) and lipopolysaccharide-stimulated mouse peritoneal macrophages. In the present study, we searched restoration drug against the inhibition of NO production by Cd in Oriental medicine. An aqueous extract of Taraxacum officinale (Compositae) (TOAE) restored the inhibition of NO production by mouse peritoneal macrophages pretreated with Cd in a dose-dependent manner. The effect of TOAE was mainly dependent on TOAE-induced tumor necrosis factor-alpha (TNF-alpha) secretion. These results suggest that the capacity of TOAE to restore NO production from interferon-gamma (IFN-gamma)-primed mouse peritoneal macrophages is the result of TOAE-induced TNF-alpha secretion.
TL;DR: It is suggested that low-level chronic MeHg exposure may cause immune disfunction by disturbing thiol redox balance, transmembrane signaling and splenic cellularity.
Abstract: Methylmercury (MeHg) is a known toxicant and continues to be a significant environmental contaminant. While the neurotoxicity and developmental toxicity of MeHg are well established, the immunotoxic effects of MeHg are just now being studied and described. This study evaluated strain and gender specific effects of low level, prolonged MeHg exposure in mice. Mice were exposed to MeHg in the drinking water (0, 3 or 10 ppm) for 4 weeks. Splenocytes and thymocytes were evaluated for alterations in immunophenotype, GSH levels, and intracellular Ca2+ flux after mitogen stimulation. MeHg exposure resulted in alterations in splenocyte and thymocyte subsets and a dose dependent decrease in GSH levels (as measured by monochlorobimane fluorescence and flow cytometry) of all splenocyte subsets. This decrease in GSH was further confirmed by biochemical assay in splenocytes. In addition, there was a dose response related decrease in mitogen stimulated Ca2+ flux and in the percentages of CD4+ splenocytes and CD8...
TL;DR: These herbal components were suggested to have a main role in the protective effect of Juzen-taiho-to against Candida infection.
Abstract: Protective effects of a kampo medicine, Juzen-taiho-to (TJ-48) and its herbal components against experimental candidiasis in cyclophosphamide-induced immunosuppressive mice were investigated. ICR mice were immunosuppressed by intraperitoneal treatment with cyclophosphamide (day-4) and were orally given TJ-48 or one of its 10 herbal components for 4 consecutive days (day-4-1). They were then challenged intravenously with a lethal dose of Candida albicans (day 0). An oral dose of 1g/kg/day of TJ-48 prolonged their life span. A similar protective effect was obtained by treatment with its component drugs Ginseng radix, Glycyrrhizae radix, Atractylodis lancea rhizoma or Cnidii rhizoma. These herbal components were suggested to have a main role in the protective effect of Juzen-taiho-to against Candida infection.
TL;DR: The probable mechanism underlying the protective action of Ashwagandha against systemic Aspergillus infection was discussed in relation with its possible activity to activate the macrophage function.
Abstract: Therapeutic efficacy of an Indian Ayurvedic medicinal preparation, Ashwagandha [Withania somnifera L. Dunal (Solanceae; root)] was evaluated against experimental aspergillosis in Balb/c mice. Ashwagandha given orally once daily for 7 consecutive days in a dose of 100 mg/kg after intravenous infection of Aspergillus fumigatus prolonged the survival period of infected mice. This protective activity was probably related to the observed increases in phagocytosis and intracellular killing of peritoneal macrophages induced by Ashwaganda treatment. The number of peripheral leukocytes was not modified, excluding a possibility of mobilization of cells from other compartments. On the basis of these findings, the probable mechanism underlying the protective action of Ashwagandha against systemic Aspergillus infection was discussed in relation with its possible activity to activate the macrophage function.
TL;DR: Results demonstrated that taxol provides two signals, "priming" and "enhancing", to generate superoxide anion via the stabilization of microtubules in murine RAW264.7 cells.
Abstract: Taxol, an anticancer drug, has been known not only to block cell division by stabilizing microtubules but also to activate murine macrophages to express TNF-α, interleukin-1, and to produce nitric oxide (NO). We therefore reasoned that taxol could activate murine macrophages to generate reactive oxygen intermediates, such as superoxide anion (O2), which are responsible for intracellular killing of pathogenic microbes. Treatment of RAW264.7 cells, murine macrophage cell line, with taxol increased phorbol ester-induced O2- production in a dose dependent manner (∼2 fold). In addition, taxol rapidly (< 1 hr) primed RAW264.7 cells to enhance O2- release stimulated with PMA. Taxol also enhanced stimulation of O2- production by FMLP, but not by Con A. This effect was abolished by prior treatment with both superoxide dismutase (SOD) and N-acetyl-L-cystein, a free radical scavenger. To investigate the mechanism of taxol-induced macrophage stimulation, we evaluated the ability of colchicine, a drug that inh...
TL;DR: Findings suggest the possible relevance of cytoskeletal affecting compounds in the modulation of FMLP-stimulated O2- release during senescence, and interestingly, elderly neutrophil function was negatively modulated by both microtubule affecting compounds.
Abstract: Several reports have emphasized that aged polymorphonuclear cells (PMN) exhibit an impairment of superoxide anion (O-2) generation when triggered with formyl-methionyl-leucine-phenylalanine (FMLP) in comparison to the younger counterpart. Since microfilaments and microtubules are involved in PMN-mediated functions, in a group of old donors we assessed the effects of either actin stabilizing and disrupting agents, i.e. phalloidin and cytochalasin B, or microtubule stabilization or disruption by taxol and colchicine, respectively, on FMLP-triggered neutrophil oxidative responsiveness. Results show that phalloidin treatment, at a concentration ranging from 10-6 to 10-8 M, gave rise to an inhibition of O-2 release by aged PMN, while the same effect was seen in similarly treated young cells at a concentration of 10-7 M only. On the contrary, cytochalasin B pretreatment led to an enhancement of O-2 generation in both young and aged neutrophils, even if to a lower extent in the latter group. At the same ...
TL;DR: Findings might be related to a derangement in the antioxidant mechanisms and to some interference with GSH levels that might lead to the abnormal functions observed in neutrophils.
Abstract: Phagocytosis and intracellular killing of Candida albicans and Candida pseudotropicalis by neutrophils from 66 workers exposed to chlorinated compounds were studied. Phagocytosis with both antigens was normal in all the workers studied. However, lytic activity of the neutrophils in the presence of both antigens, C. albicans and C. pseudotropicalis was impaired. These findings might be related to a derangement in the antioxidant mechanisms and to some interference with GSH levels that might lead to the abnormal functions observed in neutrophils.
TL;DR: Findings appear to suggest that PLD-derived phosphatidate is not the primary source of DAG production in IFN-gamma-induced TNF-alpha secretion, but may be necessary forIFN-Gamma-mediated MHC class II induction and IL-1 beta production in human monocytes, whereas phospholipase A2 may not be required for IFN -gamma activation of PKC in the process.
Abstract: This study was undertaken to investigate the effects of propranolol, IFN-beta, and the protein kinase modulators on IFN-gamma induction of MHC class II antigen expression and cytokine production in THP-1 human monocytic cells. IFN-gamma induced expression of HLA-DR and DQ molecules and secretion of the monokines IL-1 beta and TNF-alpha in THP-1 cells in a time and dose-dependent manner. The effect of INF-gamma on class II HLA antigens was dose-dependently inhibited by IFN-beta. H-7, phloretin, staurosporine as well as GF 109203X are selective enzyme inhibitors of protein kinase C (PKC), down-regulating IFN-gamma induced MHC class II expression and cytokine production. Stimulators of PKC, like PMA, replaced IFN-gamma in the induction of monokines in THP-1 cells, whereas the addition of HA 1004 or arachidonic acid to the culture had no effect on IFN-gamma mediated changes. Blocking of phospholipase D (PLD)-derived diacylglycerol (DAG) formation by propranolol abrogated IFN-gamma increased HLA class II expression and IL-1 beta secretion, but had little effect on IFN-gamma induced TNF-alpha production. These findings appear to suggest that PLD-derived phosphatidate is not the primary source of DAG production in IFN-gamma-induced TNF-alpha secretion, but may be necessary for IFN-gamma-mediated MHC class II induction and IL-1 beta production in human monocytes, whereas phospholipase A2 may not be required for IFN-gamma activation of PKC in the process.
TL;DR: It is concluded that SLAE directly affect IgE-mediated anaphylactic reaction and substance P-induced HDC mRNA over-expression, and dose-dependently inhibited histamine release in mouse peritoneal mast cells activated by anti-DNP IgE or substance P.
Abstract: We investigated the effect of aqueous extract of Soloanum lyratum THUNB. (Solanaceae) (SLAE) on anaphylactic reaction. The mast cell is widely thought to contribute to the acute changes associated with anaphylaxis. SLAE inhibited skin mast cells-mediated anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. SLAE dose-dependently inhibited histamine release in mouse peritoneal mast cells activated by anti-DNP IgE or substance P. Substance P increased steady state levels of L-histidine decarboxylase (HDC) mRNA in mouse mastocytoma P-815 cells. Northern-blot analysis demonstrated that significantly reduced level of the mRNA of HDC was expressed in mast cells treated with SLAE, compared to that without SLAE. We conclude that SLAE directly affect IgE-mediated anaphylactic reaction and substance P-induced HDC mRNA over-expression.
TL;DR: It is confirmed that endotoxin possesses immunomodulatory activities capable of stimulating immune functions both in vitro and in vivo.
Abstract: Previous studies have shown that endotoxin potentiates immune responses by direct stimulation of B cells and macrophages. In the present study, we assessed the ability of endotoxin to stimulate cells from different lymphoid tissue compartments to release cytokines. The in vitro stimulation of macrophages with endotoxin resulted in the production of IL-1 and TNF-$aL in a dose and time-dependent manner. Endotoxin also induced the production of IL-2, IFN-γ and IL-4 secretion in a dose dependent manner in cultured spleen, mesenteric lymph nodes and Peyer's patches cells. The intraperitoneal administration of endotoxin in mice resulted in the accumulation of leucocytes in the peritoneal cavity and in the increase of IL-1, IL-6, TNF-$aL and IFN-γ concentration in serum. In conclusion, this study confirmed that endotoxin possesses immunomodulatory activities capable of stimulating immune functions both in vitro and in vivo.
TL;DR: In Leishmania infantum-infected macrophages, nitric oxide production was observed at a concentration significantly higher after stimulation with both Con A-activated PBMC supernatants and LPS than that observed in uninfected cells cultured in medium alone, or infected cells unstimulated or stimulated by PBMCsupernatants or LPS alone, respectively.
Abstract: Protozoa of the genus Leishmania (L.) infect reticuloendothelial cells of several mammalian species, including dogs, in which they often give rise to a chronic, not self-healing visceral disease Since the parasitocidal mechanism of macrophages towards Leishmania in dog has not yet been well investigated, in this work we have evaluated in Leishmania infantum-infected macrophage cultures from 10 healthy dogs, killing capacity and nitric oxide (NO) production, in terms of nitrite (NO2-) levels. Parallel experiments were performed on macrophages stimulated with both Concanavalin A (ConA)-activated PBMC supematants and Salmonella typhimurium lipopolysaccharide (LPS), and in the same conditions, but in the presence of the NO synthase inhibitor L-N monomethylarginine (L-NMMA). In L. infantum-infected macrophages, nitric oxide production was observed at a concentration significantly higher after stimulation with both Con A-activated PBMC supematants and LPS than that observed in uninfected cells cultured ...
TL;DR: There were functional variations (chemotaxis and phagocytosis) in THP-1 cells in response to LPS of oral microorganisms following stimulation with GM-CSF.
Abstract: A human THP-1 monocyte cell line culture system has been utilized to observe the effect of granulocyte macrophage colony stimulating factor (GM-CSF) supplementation with lipopolysaccharide (LPS) of oral microorganisms to stimulate monocyte/macrophage functional activity. LPS of oral microorganisms, Fusobacterium nucleatum and Porphyromonas gingivalis was produced by phenol-water extraction and characterized. The phagocytosis assay was performed using F1TC labeled Saccharomyces yeast particles. Phagocytic functional activity was observed in 10-11% of resting THP-1 cells. Treatment of THP-1 cells with LPS of F. nucleatum or P. gingivalis increased the phagocytic activity of THP-1 cells 2-3 fold. GM-CSF significantly increased phagocytosis either alone or when supplemented with LPS of F. nucleatum or P. gingivalis. A chemotaxis assay was performed using a 48 well chemotaxis chamber. Chemotactic functional activity of THP-1 cells was increased 2-fold after 4 days of treatment with GM-CSF. Stimulation of THP-1 cells with LPS of F. nucleatum or P. gingivalis significantly reduced the chemotactic activity indicating the maturation towards a fixed macrophage. There were functional variations (chemotaxis and phagocytosis) in THP-1 cells in response to LPS of oral microorganisms following stimulation with GM-CSF.
TL;DR: The CL results indicated that L. cruciata induced significant changes in light emission from whole blood phagocytes, as well as isolated PMNs, which could be caused by several compounds, such as flavonoids and/or sesquiterpenes, present in the acetonic extract.
Abstract: The effects of Lunularia cruciata (L.) Dum (Bryophyta) acetonic extract was studied in vitro by means of luminol-dependent chemiluminescence (CL) emission from human peripheral whole blood phagocytes and isolated polymorphonuclear leukocytes (PMNs). L. crudata adult thalli underwent extraction with acetone. CL emission was evaluated in an automated luminometer, measuring the oxygen free-radical production by phagocytes incubated with opsonized zymosan (OZ) or phorbol myristate acetate (PMA), in absence or in presence of various concentrations of L. crudata extract. The CL results indicated that L. crudata induced significant changes in light emission from whole blood phagocytes, as well as isolated PMNs. Its inhibitory activity was more evident when resting isolated PMNs were studied. When the cells were activated, the greatest inhibitory effect was observed with PMA. The L, crudata activity could be caused by several compounds, such as flavonoids and or sesquiterpenes, present in the acetonic ext...
TL;DR: The finding that the expression of CD80 structure positively correlates with disease histological worsening points out a role for the costimulatory pathway in the progression of liver cell injury, and outline that several factors might be involved in HCV-driven immunopathogenesis.
Abstract: The recruitment of antigen-specific lymphocytes at liver site represents a prominent feature in patients chronically infected with hepatitis C virus (HCV). However, despite the strong and multispecific response, chronic infection leads in a significant number of cases to the development of cirrhosis and hepatocellular carcinoma. The finding that the expression of CD80 structure positively correlates with disease histological worsening points out a role for the costimulatory pathway in the progression of liver cell injury. On the other hand, the demonstration of CD95 and CD95-ligand positive cells in the context of periportal areas, a pattern which is not strictly associated to HCV tissue distribution, indicates the occurrence of either virus-infected or innocent bystander hepatocyte killing. Nonetheless, the persistence of HCV, in spite of cytotoxic T lymphocyte (CTL) liver recruitment, suggests a possible in-situ imbalance of cytotoxic activities, above all referred to perforin-granzyme-dependent necrosis. Altogether, these findings outline that several factors might be involved in HCV-driven immunopathogenesis. Therefore, the fully clarification of these mechanisms may offer a suitable therapeutical approach for the improvement of clinical outcome in chronic hepatitis C.
TL;DR: Results suggest that administration of rhM-CSF not only activates murine macrophages, but modulates antigen-specific immune responses in vivo.
Abstract: We examined the effects of recombinant human M-CSF (rhM-CSF) on mouse macrophages and immune responses in vivo. Intraperitoneal administration of rhM-CSF (20-500 microgram/ml) increased Mac-1+ cell numbers in the peritoneal cavity. The tumoricidal activities of the macrophages from vehicle-administered (V-M phi) and from rhM-CSF-administered (M-M phi) mice were the same as those observed in vitro. However, when activated by lipopolysaccharide (LPS), the tumoricidal activity of M-M phi was stronger than that of V-M phi. Intravenous administration of rhM-CSF (500 micrograms/gk) increased the number of spleen cells. Flow cytometric analysis showed that administration of rhM-CSF increased Mac-1+, B220+ and NK 1.1+ cell counts in the spleen. However, CD4+ and CD8+ cell numbers did not change. Concomitant increases were observed in levels of IL-4 and IL-10 in mouse serum following rhM-CSF administration, but no significant changes were observed in the serum level of IFN-gamma. In experiments involving mouse immune responses, the administration of rhM-CSF reduced the contact sensitivity (CS) reaction against picryl chloride (PC) and augmented IgE production in response to 2,4-dinitrophenyl (DNP), but did not affect the production of either IgM or IgC1. These results suggest that administration of rhM-CSF not only activates murine macrophages, but modulates antigen-specific immune responses in vivo.
TL;DR: The selective, antigen specific augmentation of human T cell response suggests that Picroliv could be useful as an adjunct to chemotherapy or as a short term prophylactic agent.
Abstract: Mycobacterial and other intracellular parasitic diseases are characterised by a deficiency in antigen specific host T cell responses. We have studied the effect of Picroliv, a standardised fraction of root and rhizome of Picrorhiza kurroa, on proliferative T cell response to the mycobacterial ‘Purified Protein Derivative (PPD)’ antigen in subjects infected with or exposed to mycobacteria (tuberculoid leprosy patients and endemic normals). Coculture of their peripheral blood mononuclear cells with the optimal concentration of Picroliv (0.5 μg/ ml) significantly enhanced the proliferative response to 1/10 optimal PPD dose, as determined by [3H] thymidine incorporation, in the group of ‘low’ responders. The response to PPD of cells from ‘high responders’ and to PHA (phytohaemagglutinin, a non-specific T cell mitogen) remained unaffected by Picroliv which did also not induce cell proliferation on its own. The selective, antigen specific augmentation of human T cell response suggests that Picroliv coul...
TL;DR: The findings confirm the occurrence of an immune activation status during chronic hepatitis C and suggest that sHLA-I molecules might play a down-modulating role on immunoresponsiveness of these patients.
Abstract: In the present study, intrahepatic CD8+ lymphocyte infiltrates as well as HLA class I and CD54 (ICAM-1) antigen expression at both tissue and serum levels were evaluated in 54 untreated patients with chronic hepatitis C stratified on the basis of histological diagnosis (Chronic Persistent Hepatitis/Chronic Lobular Hepatitis-CPH/CLH-and Chronic Active Hepatitis-CAH-: 22 and 32 subjects, respectively). The relationships between soluble HLA-I (sHLA-1) and ICAM-1 (sICAM-1) serum levels and their membrane-bound counterparts, CD8+ liver infiltration and serum alanine aminotransferase (ALT) were also studied.A strong HLA-I and CD54 tissue expression, associated to the presence of CD8+ cell infiltrates in necro-inflammatory areas, and elevated sHLA-1 and sICAM-1 serum amounts were observed in all patients. At the same time, no difference was found at tissue level between the two groups of patients with respect to the mean scores of HLA-I and CD54 expression, while CAH subjects displayed a significantly hi...
TL;DR: A 44-year-old woman with a delayed hemolytic transfusion reaction (DHTR), who had a history of two pregnancies and a blood transfusion, screened for anti-RBC Abs, which were detected in blood samples obtained from the patient on March 12, 1996.
Abstract: We describe the case of a 44-year-old woman with a delayed hemolytic transfusion reaction (DHTR). She had a history of two pregnancies and a blood transfusion, the details of which were unknown. At the time of her first vascular surgery on November 15, 1989, she received 1200 ml of crossmatch-compatible concentrated red blood cells (CRC). Before the first operation, screening for anti-RBC antibodies (Ab) was negative. At the time of the second admission on Feburary 15, 1996, anti-E Abs were detected by indirect antiglobulin test. She received 560 ml of E-antigen-negative, crossmatch-compatible, CRC for treatment of anemia on March 1 and 2, 1996. After this transfusion, total bilirubin (1.6 mg/dl) and lactate dehydrogenase (1355 IU/ml) were elevated on March 12, 1996. She had no evidence of clinical hemolysis. We suspected DHTR from these data, and therefore screened for anti-RBC Abs. Anti-E, Jka, Dia, Fyb, and S Abs were detected in blood samples obtained from the patient on March 12, 1996. Anti-E...
TL;DR: In 55% PVS male patients hyperprolactinemia was observed, whereas in outcome patients more than six months these values were within normal range, and in four patients, who emerged from coma in the course of this study, prolactin plasma levels were followed-up and increased basal values progressively fell to normal range within six months.
Abstract: Hypothalamic-pituitary-adrenocortical hormones, i.e. prolactin (PRL), human growth hormone (hGH), thyroid stimulating hormone (TSH), and Cortisol and plasma levels of cytokines, i.e. tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and interleukin-6 (IL-6), were assessed in 27 patients with persistent vegetative state (PVS) and in 16 outcome patients. In comparison with normal parameters, plasma levels of TSH were not significantly altered, while elevated basal hGH concentrations in 48.1% of PVS subjects and depressed cortisol levels in all PVS individuals and in patients who emerged from coma (outcome patients), respectively, were observed. In addition, higher TNF-α plasma levels in PVS subjects than in outcome patients and in healthy donors were found, while IL-1β plasma levels were elevated in both groups of patients in comparison with healthy controls. Of interest, in 55 % PVS male patients hyperprolactinemia was observed, whereas in outcome patients more than six months these values w...