Showing papers in "Immunopharmacology and Immunotoxicology in 1986"
TL;DR: The pharmacokinetics of murine tumor necrosis factor in mice as a model for application in the human system can provide parameters by which to select optimal modes of treatment for eradication of in vivo neoplasms.
Abstract: The in vivo administration of tumor necrosis factor (TNF) provides a new approach to the immunotherapeutic treatment of tumors. We evaluated the pharmacokinetics of murine tumor necrosis factor in mice as a model for application in the human system. TNF had a clearance of 0.013 ml/min/g and a serum half life of 10.5 minutes. Its volume of distribution was consistent with the extracellular space. This information can provide parameters by which to select optimal modes of treatment for eradication of in vivo neoplasms.
50 citations
TL;DR: The flavonoids quercetin and tangeretin are most effective when added during the early phase of exposure of lymphocytes to the mitogenic stimuli but become progressively less effective whenadded after increasing lengths of time following stimulation, suggesting an early flavonoid-sensitive step(s) in cell activation.
Abstract: A number of representative flavonoids reversibly inhibit human lymphocyte proliferative responses in a concentration-dependent manner The flavonoids quercetin and tangeretin are most effective when added during the early phase of exposure of lymphocytes to the mitogenic stimuli but become progressively less effective when added after increasing lengths of time following stimulation, suggesting an early flavonoid-sensitive step(s) in cell activation In the proliferative response to phytomitogens, they do not act by inhibiting the early increase in calcium influx They do not augment cellular cyclic-AMP concentration in basal or phytomitogen-stimulated lymphocytes nor reduce its increment in the presence of inhibitors of phosphodiesterase At concentrations inhibitory to the proliferative response, quercetin (but not tangeretin) inhibits the calcium-activated, phospholipid-dependent protein kinase (C kinase) Certain flavonoids powerfully inhibit the uptake of thymidine into phytomitogen-stimulate
32 citations
TL;DR: In contrast to glucan-P, however, intravenous glucAn-F administration has been shown not to induce granuloma formation and severe hepatosplenomegaly, thus the potential clinical use of glucan (glucan-F) as a hemopoietic stimulant is more likely than that of glucose-P.
Abstract: A soluble form of the reticuloendothelial- and immune modulating agent glucan (glucan-F) has been evaluated for its effects on hanopoiesis. A single 5.0 mg intravenous injection of glucan-F into C3H/HeN mice increased peripheral white blood cellularity, bone marrow and splenic cellularity, bone marrow and splenic granulocyte-macrophage progenitor cell numbers (GM-CFC), and splenic pluripotent stem cell (CFU-s) and erythroid progenitor cell (CFU-e) numbers. Serum levels of granulocytemacrophage colony stimulating activity (CSA) were also elevated following glucan-F administration. These hemopoietic responses correlate well with those previously shown to be induced by intravenous administration of particulate glucan (glucan-P). In contrast to glucan-P, however, intravenous glucan-F administration has been shown not to induce granuloma formation and severe hepatosplenomegaly, thus the potential clinical use of glucan-F as a hemopoietic stimulant is more likely than that of glucan-P.
30 citations
TL;DR: This in vitro system will facilitate manipulations of T and B lymphocytes and macrophages in a controlled culture environment for precisely characterizing the sensitivity of these cells and their subpopulations on exposure to BaP.
Abstract: The effect of benzo(a)pyrene (BaP) at different molar (MI concentrations on the in vitro anti-sheep red blood cell (SRBC) plaque (antibody) forming cell (PFCI response and the one-way mixed lymphocyte response (MLR) was tested. Inhibition of the PFC response and the MLR occurred when spleen cells were exposed to a wide range of BaP concentrations from 10–4 m to 10–8 m. Maximum depression of the responses occurred at 10–5 M for PFC production (47% of controls) and for the MLR (19% of controls) as measured by a stimulation index. No significant loss in cell viability was observed at this or lower molar concentrations of BaP. The non-carcinogenic analog of BaP, benzo(e)pyrene, did not suppress PFC responses at comparable concentrations. This in vitro system will facilitate manipulations of T and B lymphocytes and macrophages (adherent cells) in a controlled culture environment for precisely characterizing the sensitivity of these cells and their subpopu-lations on exposure to BaP.
25 citations
TL;DR: It was shown that the stereodifferentiation of anti-tumor effect of enantiomers was not outstanding although quite consistently in favour of levorotatory forms.
Abstract: The relationship between enantiomeric homogeneity of three oxazaphosphorine drugs: cyclophosphamide, ifosfamide and trofosfamide and their antitumor activity was evaluated by standard screening tests against four in vivo transplantable tumor models: L 1210 and P 388 lymphoid leukemias, Lewis lung carcinoma and 16/C line of mouse mammary adenocarcinoma. It was shown that the stereodifferentiation of anti-tumor effect of enantiomers was not outstanding although quite consistently in favor of levorotatory forms. The only exception was seen for cyclophosphamide enantiomers tested against leukemias where R/+/ form was more effective than S/-/ or racemate.
23 citations
TL;DR: The results may suggest that m1Ado is a major factor in tumor ascites causing, in small doses, an impairment of macrophage functioning as can be detected in tumor-bearing hosts.
Abstract: The low molecular weight fraction (mol wt < 1,000) of Ehrlich cancer ascitic fluid has been known to enhance Listeria infection in mice. Chemical characterization of the entities in this fraction revealed four purine and pyrimidine analogues, i.e. uric acid, uracil, pseudouridine and 1-methyladenosine (m1Ado). When the effect of each of these components was studied on Listeria infection in mice, only m1Ado markedly enhanced the infection and killed the mice within a short period. The optimal enhancement was obtained when m1Ado was given intravenously to mice 3-6 days before the infection at a concentration of between 1 and 100 μg/mouse. On the other hand, uric acid, uracil and pseudouridine failed to show such an enhancing effect. m1Ado inhibited macrophage accumulation in the peritoneal cavity of mice after an intraperitoneal injection of phytohemagglutinin. Although m1Ado did not show any inhibitory effect on the phagocytic and bactericidal activities of macrophages in vitro.
22 citations
TL;DR: Results indicate that prostaglandins are involved in the regulation of hematopoiesis in untreated mice and that prostagslandins may limit the hematoietic recovery of CY treated mice.
Abstract: Indomethacin (IN) was administered to untreated or to cyclophosphamide (CY) treated C57B1/6 mice to study the roles of prostaglandins in regulating hematopoiesis. The following hematopoietic parameters were quantitated: peripheral blood leukocyte (PBL) count; total nucleated cells per spleen; total nucleated cells per femur; and spleen weight. Assays were performed in vitro to measure the number of colony forming units (CFU) present in the bone marrow and spleen. Untreated mice administered IN had a transient rise in their PBL count. These animals also developed splenomegaly and had an increased number of nucleated cells in their spleen. All CY treated mice had a marked decrease in PBL count, spleen cellularity, bone marrow cellularity, and spleen size during the first 5 days after CY treatment. These observations were followed by hematopoietic recovery over the next 10 days. Cyclophosphamide treated mice exhibited a more rapid hematopoietic recovery when treated with IN than without IN treatment. Analysis of the CFU capacity of bone marrow and spleen cells in soft agar showed a larger number of CFU in the bone marrow and spleen of IN treated mice or of CY/IN treated mice than in animals not receiving IN. These results indicate that prostaglandins are involved in the regulation of hematopoiesis in untreated mice and that prostaglandins may limit the hematopoietic recovery of CY treated mice.
22 citations
TL;DR: In healthy subjects OM-89 seems to act mainly on the cell-mediated immune responses, while the in vitro investigation showed that it is not a mitogen.
Abstract: APSTRACTA lyophilized extract from F. coli (0M-89) was studied for its immunomodulating properties and tolerance in humans. Its oral administration to healthy volunteers produced a selective increase in the active T-cell population without changes in other lymphocyte populations. A significant increase in the proliferative response to concanavalin A and phytohemaaqlutin was recorded, hut not to pokeweed mitogen. No significant changes were observed in the serum levels of IgG, IgA and IgM. The clinical and biological tolerance of OM-89 was excellent, without any adverse side-effects or production of circulating immune complexes or of autoantibodies, while the in vitro investigation showed that it is not a mitogen. Thus in healthy subjects 0M-89 seems to act mainly on the cell-mediated immune responses.
21 citations
TL;DR: It was revealed that the increased lymphocyte subpopulations not only in the peritoneal cavity but also in the spleen of C3H/He mice by the injection of shosaiko-to were comprised of both immature B (IgM+ and IgD-) and null (thyl- and Ig-) cells.
Abstract: Accumulation of lymphocytes after an intraperitoneal (ip) injection of a traditional Chinese herb medicine, XIAO-CHAI-HU-TANG (Japanese name : shosaiko-to), was investigated. Shosaiko-to induced marked accumulation of lymphocytes rather than macrophages in the peritoneal cavity of ICR mice, whereas various kinds of irritants, e.g. proteose-pepton, Escherichia coli lipopoly-saccharide (LPS), OK-432 and Corynebacterium parvum, induced preferential accumulation of macrophages rather than lymphocytes. By means of analysis using two-color fluorescence-activated cell sorter (FACS), it was revealed that the increased lymphocyte subpopulations not only in the peritoneal cavity but also in the spleen of C3H/He mice by the injettion of shosaiko-to were comprised of both immature B(IgM+ and IgD−) and null (thyl− and Ig−) cells. This effect of shosaiko-to was observed in other C5 normal strains, C3H/HeJ (LPS-nonresponder), C57BL/6, BALB/c and athymic nu/nu (ICR background) mice, but not in C5 deficient strain...
20 citations
TL;DR: It is indicated that multiple intracellular pathways of AA metabolism are present HT-2 cells, and that the stimulus-induced release of AA and the production of eicosanoid second messengers may result from activation of either phospholipase A2 or phospholIPase C.
Abstract: Previous studies have provided pharmacologic evidence that T lymphocyte function may be regulated in part by the intracellular production of various arachidonic acid (AA) metabolites in response to cellular stimulation. However, the specific AA metabolic capabilities of homogeneous T cell populations have not been clearly defined. In the present studies, we have employed an accessory cell-free T cell line, HT-2, as a model system for the examination of stimulus-induced eicosanoid biosynthesis in T lymphocytes. HT-2 cells were biosynthetically labeled with [3H]-AA and challenged briefly with various agents that stimulate the hydrolytic release of AA from cellular phospholipids. The bee venom peptide melittin stimulated a profound AA release response in the cells and the concomitant synthesis of both cyclooxygenase (PGF2 alpha, PGE2 and PGD2) and lipoxygenase (5-,12-,15-HETE and possibly 5-,12-diHETE) metabolites of AA. The formation of PGs was blocked by 5 microM indomethacin, demonstrating that this cell line contains cyclooxygenase activity functionally similar to that described in macrophages and other cell types. The high activity of melittin in this system was shown to result largely from a synergy between the peptide itself and a persistent bee venom phospholipase A2 contaminant. However, experiments with melittin freed of detectable phospholipase A2 activity by heating, and with synthetic homopolymers of (L)-lysine and (L)-arginine demonstrated that HT-2 cells contain sufficient endogenous, stimulus-responsive phospholipase A2 to provide both the cyclooxygenase and lipoxygenase pathways of AA metabolism ith substrate. In contrast, Ca++ ionophores, which are known to stimulate AA release and metabolism in certain cell types, stimulated only AA release but no detectable eicosanoid biosynthesis in HT-2 cells. Experiments with exogenous bacterial phospholipase C suggested that this cell line can also generate free AA for eicosanoid biosynthesis from membrane-derived 1,2-diacylglycerol. These results indicate that multiple intracellular pathways of AA metabolism are present HT-2 cells, and that the stimulus-induced release of AA and the production of eicosanoid second messengers may result from activation of either phospholipase A2 or phospholipase C.
19 citations
TL;DR: The therapeutic effect of endogenous tumor necrosis factor on Meth A ascites fibrosarcoma in mice was investigated and results indicate that endogenous TNF has a satisfactory life-prolonging effect.
Abstract: The therapeutic effect of endogenous tumor necrosis factor (TNF) on Meth A ascites fibrosarcoma in mice was investigated. Serum and peritoneal fluid from tumor bearing mice treated with OK-432 and LPS were cytotoxic to tumor cells in vitro. The peak of cytotoxicity in both the serum and peritoneal fluid was found in the fraction corresponding to a molecular weight of approximately 54,000-56,000 on HPLC and the pI was found to be 4.9-5.1 by isoelectric focusing. These results are consistent with previously reported findings on TNF, and indicate that endogenous TNF has a satisfactory life-prolonging effect. The tumor necrosis factor (TNF) is considered to be one of the clinically most promising anti-cancer cytokines because of its potent and very specific antitumor effect on target cells (Carswell, Old, Kassel, Green, Fiore & Williamson, 1975; Matthews & Watkins, 1978; Niitsu, Watanabe & Urushizaki, 1984). TNF as an anti-cancer cytokine for the treatment of cancer may be applied in one of the two following ways: by administration of purified TNF or by endogenously inducing TNF in cancer bearing individuals. The antitumor effects of TNF administered exogenously have been examined using crude preparations or serum containing TNF (tumor necrosis serum, TNS) (Carswell et al., 1975; Watanabe, Niitsu, Sone, Neda, Ishigaki & Urushizaki, 1984). In a previous paper we reported that mice primed with OK-432 and challenged with endotoxin produced a soluble cytotoxic factor in peritoneal fluids (Yamamoto, Nagamuta, Usami, Sugawara, Watanabe, Niitsu & Urushizaki, 1985; Nagamuta, Yamamoto, Usami, Sugawara, Watanabe, Niitsu & Urushizaki, 1985). Ths peritoneal cytotoxic factor (PCF) had cytostatic and/or cytotoxic effect not only on mouse tumor cell lines but also on human tumor cell lines without species specificity. Normal cell lines were not affected. Here we report the endogenous production of TNF in tumor bearing mice and its antitumor effects.
TL;DR: Cyclosporine A (CsA), one compound in the family of cyclosporines, has effectively modulated the course of S-antigen induced experimental autoimmune uveitis (EAU) and is felt to be markedly less nephrotoxic than CsA, the secondary effect that is most commonly encountered, and could potentially be useful in the treatment of human intra-ocular inflammatory disease.
Abstract: Cyclosprine A (CsA), one compound in the family of cyclosprines, has effectively modulated the course of S-antigen induced experimental autoimmune uveitis (EAU). Cyclosporines G (CsG) and D (CsD), related to CsA in structure, were evaluated in their ability to prevent or modulate EAU in Lewis rats. 10 mg/kg/day IM of CsA effectively prevented the expression of EAU hen therapy began on the day of immunization, while the same dosage of CsG prevented EAU in 81% of animals, and CsD only in 33%. Higher concentrations of CsG (40 mg/kg/day) did effectively block manifestations of the disease. Topical administration of CsG did not prevent the expression of disease but local protection was seen when the 500 ug CsG was placed intracamerally into only one eye. The in vitro comparison of these cyclosprines’ capacity to alter proliferation and IL-2 release of a rat T-cell line capable of inducing EAU showed marked differences. CsA appeared to be mst effective at abrogating these cellular functions at all conce...
TL;DR: It is concluded that ciamexone seems to influence the autoimmune state of the BB rat resulting in partial suppression of the disease.
Abstract: BB rats spontaneously develop an insulin dependent diabetes which resembles in many features human type I diabetes. We have tested the effect of the immunomodulatory drug Ciamexone, a 2-cyan-aziridine-derivative, on the development of diabetes in BB rats. Ciamexone was given once daily during 6 days per week beginning with the age of 42 or 50 days up to 120 days. For comparison cyclosporin A (10 mg/kg) was applied following the same protocol. At 1 mg/kg ciamexone administration led to complete prevention of diabetes in females but was not beneficial in males. At 10 mg/kg the drug caused significant suppression of diabetes development in males but more pronounced in females. Both, a reduction of the incidence of diabetes and a delay in the onset of hyperglycaemia was observed only in females. After administration of cyclosporin A none of the animals developed diabetes.Ciamexone treatment did not affect granulocyte and lymphocyte counts and subsets in the peripheral blood except for a tendency to su...
TL;DR: In an experimental metastasis model, subcutaneous or intraperitoneal treatment with FK-565 markedly inhibited lung metastasis formation when administered 2-4 days prior to i.v. tumor inoculation, suggesting that activated macrophage were responsible for the antimetastatic activity of Fk-565.
Abstract: Resident peritoneal macrophages can be activated to develop cytotoxicity against P815 mastocytoma target cells following incubation in vitro with either D-lactoyl-L-alanyl-γ-D-glutamyl-(L)-meso-diaminopimelyl-(L)-glycine (FK-156), heptanoy1-γ-D-glutamyl-(L)-meso-diaminopimelyl-(D)-alanine (FK-565), or bacterial lipopolysaccharide (LPS) at a minimum concentration of 10 µg/ml. Subthreshold levels of hybridoma-derived macrophage activating factor (MAF) markedly potentiated this activity. In an experimental metastasis model, subcutaneous or intraperitoneal treatment with FK-565 (1 to 10 mg/kg) markedly inhibited lung metastasis formation when administered 2–4 days prior to i.v. tumor inoculation. Moreover, this protective activity could be abrogated by the selective macrophage inhibitor, 2-chloroadenosine, suggesting that activated macrophage were responsible for the antimetastatic activity of FK-565.
TL;DR: Evidence is provided that adjuvant- induced arthritis and type II collagen-induced arthritis are distinct entities, and that they may be discriminated by the nature of the humoral response.
Abstract: Systemic and local immunological responses of rats sensitized with either M. butyricumor native type II collagen have been evaloatod. In rats exhibiting adjuvant-induced arthritis no antibodies to collagen could be detected. In animals exhibiting collagen-induced arthritis, high antibody titsrs developed by day 14, and could be correlated with the severity of the arthritis.Delayed type hypersensitivity (DTH) responses were measured by a 5-iodo-2′-deoxyuridine 125-I (125-IUdR) uptake assay. Arthritic scores in rats immunized with collagen were not accompanied by a positive DTFt response, where as adjuvant arthritic rats showed a positive response. T-lymphocyte cellular responses in both adjuvant- and collagen-induced arthritic rats were measured. In neither syndrome were major alterations observed in T-lymphocytz subpopulations. These results provide evidence that adjuvant-induced arthritis and type II collagen-induced arthritis are distinct entities, and that they may be discriminated by the natur...
TL;DR: Findings suggest that angiotensin II may inhibit mononuclear cell thymidine uptake through stimulation of suppressor lymphocytes contained within the OKT8+ subpopulation.
Abstract: Recent evidence suggests that anglotens in II may participate in the regulation of Inflammation. We previously reported that anglotens in II in bits its human peripheral blood mononuclear cell reactivity and acts directly on lymphocytes. These observations are again confirmed. In addition, purified OKT8+ but not OKT4+ T cell suspensions stimulated with phytohemagg uniting revealed Increased thymidine incorporation when simultaneously cultured for 48 hours with angictensin II. These findings suggest that anglotens in II may Inhibit mononuclear cell thymidlne uptake through stimulator of suppresser lymphocytes contained within the OKTE+ subpopulation.
TL;DR: Results indicate that marked differences in immunopharmacologic effects may be observed if chemical exposure occurs at different times during the ontogeny of the immune system.
Abstract: Administration of urethan (URE or ethyl carbamate) to mice results in the development of a variety of tumors, and, in certain strains of mice, marked suppression of the immune response. Perinatal exposure of mice to URE has been found to result in increased tumor induction compared to exposure of adult animals. In the present study, the effects of perinatal exposure to URE on the development of immunocompetence was investigated. Pregnant mice were injected with total doses of either 0.5 or 1.0 mg URE/g of body weight over days 7-16 of gestation or pups of nontreated dams were administered a total dose of 2.0 mg URE/g of body weight over postpartum days 5-14. Postnatal exposure to URE suppressed NK (natural killer) cell activity but left intact other measured parameters of the host defense system. Prenatal exposure, on the other hand, resulted in elevated leukocyte counts and a trend toward increased spleen and thymus size in offspring of treated mothers. Humoral immune function, as measured by the IgM response to sheep erythrocytes, was suppressed in pups from dams injected with a total of 1.0 mg/g URE. These results indicate that marked differences in immunopharmacologic effects may be observed if chemical exposure occurs at different times during the ontogeny of the immune system.
TL;DR: Mouse splenic lymphocytes exposed to CP, either in vivo or in vitro, developed morphological changes consistant with the induction of phospholipidosis, and CP induced functional changes in lymphocytes, providing evidence for a relationship between this phenomenon and altered immune function.
Abstract: With repeated administration to animals, the cationic, amphiphilic drug, cnlorphentermine (CP), has been shown by others to induce a phospholipidosis in lymphocytes. In the present study mouse splenic lymphocytes, exposed to CP, either in vivo or in vitro, developed morphological changes consistant With the induction of phospholipidosis. In addition, CP induced functional changes in lymphocytes. Mice, treated with CP in vivo, demonstrated a significantly depressed ability to generate a delayed hypersensitivity response or to produce antibody-secreting cells against de novo antigens. Mouse splenic lymphocytes, exposed to 10−7 M CP for 3 days in vitro, demonstrated a signficantly depressed blastogenic response to the mitogens phytohemagglutinin, concanavalin A and lipopolysaccharide.CP inhibited an event that occurred early during lymphocyte activation, but was subsequent to mitogen/receptor coupling. In addition, CP significantly depressed the increased uptake of choline that occurs in lymphocytes ...
TL;DR: Detailed immunological analysis of uric acid and uracil revealed that the augmenting activities of mouse and human NK cells by mouse IFN alpha/beta or human rIFN alpha A/D were impaired in the presence of either compound at concentrations of 0.07 mM, the concentration detectable in the ascitic fluid of tumor bearing mice.
Abstract: A definite increase in two low molecular weight factors, G10-2 and G10-3 was found in Ehrlich ascitic fluids, parallel to tumor growth. The isolation and identification of the two factors were attempted through gel filtration and reversed phase column chromatography, using ascitic fluids obtained 13 days after intraperitoneal implantation of Ehrlich tumor cells. As a result, two highly purified factors were observed upon examination by high performance liquid chromatography. Additional analytical data, collected by UV spectrum, NMR spectrum and mass analysis. allowed us to identify G10-2 as uric acid and G10-3 as uracil.Detailed immunological analysis of uric acid and uracil revealed that the augmenting activities of mouse and human NK cells by mouse IFNδ/β or human rIFN δA/D were impaired in the presence of either compound at concentrations of 0.07 mM, the concentration detectable in the ascitic fluid of tumor bearing mice.
TL;DR: It was demonstrated that antigen specific helper T cell activity was promoted by diazepam administration in mice and the results suggest thatdiazepam promotes the antibody response through stimulating helpers T cell functions.
Abstract: Oral administration of diazepam at doses of 5-10 mg/kg to restraint-stressed mice resulted in almost complete recovery in the stress-induced suppression of the antibody response to sheep red blood cell (SRBC). Moreover, this compound restored the suppression of antibody response to SRBC in cyclophosphamide-treated mice. Diazepam treatment also enhanced the antibody response against SRBC in normal mice only when the animals were immunized with the reduced amount of antigen. It was demonstrated that antigen specific helper T cell activity was promoted by diazepam administration in mice. Addition of diazepam augmented the in vitro anti-SRBC hemolytic plaque-forming cell (PFC) response in mouse splenocytes without altering kinetics of the response. However, the enhancing effect was observed only when the drug was added to the medium at the culture initiation. On the other hand, antibody response to T cell-independent antigens such as trinitrophenylated (TNP)-Ficoll and TNP-lipopolysaccharide were not enhanced by diazepam. Concanavalin A or LPS-induced 3H-thymidine uptake into splenocytes were not stimulated by diazepam. These results suggest that diazepam promotes the antibody response through stimulating helper T cell functions.
TL;DR: Surface markers on rat lymphocytes from thymus and T-cell areas of lymph node, spleen and Peyer's patches were examined in histological sections after one single dose of Cyclophosphamide to investigate Pan T, TH and Ts/c marker expressions.
Abstract: Surface markers on rat lymphocytes from thymus and T-cell areas of lymph node, spleen and Peyer's patches were examified in histological sections after one sinale dose of Cyclophosphamide (CY, 100 mg/kg body weight). A panel of monoclonal antbodies was used: W3/13, W3/25 and OX8 to investigate Pan T, TH and Ts/c marker expressions respectively. Ts/c marker expression showed a marked and significant reduction in both thymus and lymph node lymphocytes 3 days after CY treatment. This was followed by return to normal in the thymus and a significant rebound increase in the lymph node by day 7 after treatment. This TS/c marker expression in both the spleen and Peyer's patches showed a significant increase on both day 3 and 7 after CY treatment.Mast cells were observed in lerge numbers in the thymus and lymph node but not in the spleen and Peyer's patches. TH marker expression was increased significantly in lymph nodes, spleen and Peyer's patches. No change was observed in Pan T marker expression in any ...
TL;DR: In this article, the effect of complement components and complement fragments on human allogeneic cell mediated lympholysis (CML) was investigated and it was shown that C3 and C3b at a concentration of 275 M × 10−9 and C 3d at a level of 330 M × 9−9 enhanced human CML by at least two fold.
Abstract: Complement components and complement. breakdown products have been found to participate in the regulation of the immune response. In the present study we investigated the effect of C3 and its fragments, C3b, C3c and C3d on human allogeneic cell mediated lympholysis (CML). C3 and C3b at a concentration of 275 M × 10−9 and C3d at a concentration of 330 M × 10−9 enhanced human allogeneic CML by at least two fold. In contrast C3C did not affect CML responses. Both C3b and C3d had to be present at the initiation of the cultures in order to exert their effect. Similar doses of C3b and C3d did not affect the mixed lymphocyte responses (3H-thymidine uptake) while higher doses were clearly inhibitory. None of the preparations induced proliferative or cytotoxic responses in the absence of allogeneic stimulating cells. C3b and C3d added to the mixed lymphocyte cultures caused increased production of interleukin 2. We conclude that C3b and C3d facilitate allogeneic cytotoxic responses through increased produc...
TL;DR: Through ricin-antibody conjugation a high degree of specificity and toxicity can be attained potentially suitable for anti-tumor reagents and immuno-modulators.
Abstract: By altering the receptor binding specificity of the highly potent natural toxin ricin, a macrophage specific immunotoxin was developed. Ricin ordinarily does not demonstrate cell type specificity and is capable of binding and entering cells through galactose containing receptors resulting in rapid cell death. A murine anti-rat peritoneal macrophage IgG1 monoclonal antibody, B-6, was developed to serve as a target specific carrier for ricin. By covalently binding monoclonal antibody B-6 and reversibly binding lactose to ricin, a new biologically active hybrid toxin possessing macrophage specificity was developed. When P3X63-Ag8.653 myeloma cells, which served as an nonspecific target cell type, and macrophages were treated with the ricin conjugate over a broad range of concentrations and various time periods, the conjugate demonstrated substantially greater toxicity toward macrophages than myeloma cells even though both cell types responded similarly to treatments with unconjugated ricin. It was al...
TL;DR: There was a significant depletion noted in the number of haemopoietic progenitor cells as measured by in vitro culture, and no effect was seen on FBC's or on marrow histology.
Abstract: The effect of multiple sublethal doses of busulfan on the haemopoietic system of the Balb/c mouse was examined. FBC's bone marrow histology and bone marrow progenitor cell assays (CFU-E, BFU-E, CFU-GM and CFU-GEM) were performed. No effect was seen on FBC's or on marrow histology. However there was a significant depletion noted in the number of haemopoietic progenitor cells as measured by in vitro culture.
TL;DR: In conclusion, treatment with the beta blocker acebutolol may trigger antinuclear antibody (ANA) production, and the presence of such isolated ANA is not known to expose patients to any particular risk other than exceptional and minor clinical manifestations of lupus which are rapidly reversible following therapy cessation.
Abstract: Treatment with the beta blocker acebutolol may trigger antinuclear antibody (ANA) production. We retrospectively studied 97 sera from 47 patients who developed ANA during acebutolol treatment. Anti-histone and anti-denatured (ss) DNA antibodies were found in 53% and 66% respectively of the sera tested. The activities of these two antibodies correlated well with the total ANA titer. Anti-native (ds) DNA were absent or present at low titer. This immunochemical pattern of acebutolol-induced ANA is similar to that reported for other drug-induced ANA. To date, the presence such isolated ANA is not known to expose patients to any particular risk other than exceptional and minor clinical manifestations of lupus which are rapidly reversible following therapy cessation.
TL;DR: Stable activated macrophage hybridomas generated by somatic cell fusion between Propionibacterium acnes-induced peritoneal exudate cells and NS-1 myeloma cells should be very useful in studies on cancer immunology and the physiology of macrophages.
Abstract: Stable activated macrophage hybridomas were generated by somatic cell fusion between Propionibacterium acnes-induced peritoneal exudate cells and NS-1 myeloma cells. Five cell lines were obtained and each was cloned by limiting dilution; 59 clones were obtained. The cells of 2 clones (MP4–4 and MP4–8) which adhered to the culture dishes were selected for further analysis. These hybridomas exhibited non-specific esterase and B-galactosidase intracellularly, and asialo GM1, Mac-1, Ia antigens and Fc-receptors on their cell surface. They did not, however, show phagocytic activity or secrete lysozyme. These hybridomas (MP4–4 and MP4–8) secreted the cytotoxic factor without any stimulation. Furthermore strong cytotoxic activity was found in ascites and sera from nude mice inoculated with these hybridomas. These activated macrophage hybridomas should be very useful in studies on cancer immunology and the physiology of macrophages.
TL;DR: Therafectin (SM-1213) is a new agent which selectively activates macrophages and stimulated interleukin 1 production in vitro and was administered to 12 homosexual men without AIDS in a double-blind, placebo controlled trial, which failed to find any significant changes in their immunologic status including interleucin 1 or 2 production.
Abstract: Patients with the acquired immunodeficiency syndrome (AIDS) are susceptible to a variety of opportunistic pathogens which require intact cellular immunity for control and eradication. We evaluated interleukin 1 and 2 production in 12 homosexual men without AIDS but with evidence of altered cell-mediated immunity and serologic evidence of infection with human T-cell lymphotrophic virus type III (HTLV-III), the etiologic agent of AIDS and found production of both factors diminished compared to heterosexual controls. Therafectin (SM-1213) is a new agent which selectively activates macrophages and stimulated interleukin 1 production in vitro. Therafectin was administered to these same 12 patients in a double-blind, placebo controlled trial. We failed to find any significant changes in their immunologic status including interleukin 1 or 2 production.
TL;DR: The immunomodulatory effects of Wy-41,770, compared to levamisole and indomethacin in several in vivo models may contribute along with its antiinflammatory activity, towards the treatment of arthritic diseases.
Abstract: The immunomodulatory effects of Wy-41,770 (5H-dibenzo[a,d)cyclohepten-5-ylidene)acetic acid, were compared to levamisole and indomethacin in several in vivo models. In the Jerne plaque assay, Wy-41,770 (1 and 100 mg/kg, p.o.) administered on day 1 after sensitization suppressed IgM plaque forming cells (PFC) while levamisole was active when given on days 1 and 2 after sensitization. In contrast, indomethacin administered on days 2 and 3 after sensitization increased PFC. In the rat experimental allergic encephalomyelitis (EAE) model, Wy-41,770 reduced limb paralysis at 10 and 100 mg/kg, p.o. when dosed before sensitization. Indomethacin was active too when predosed in the rat EAE model. In the methylated bovine serum albumin model (MBSA) delayed hypersensitivity (DH) model in mouse, Wy-41,770 (10 mg/kg, p.o.) given on day 1 prior to sensitization and day 2 after sensitization in subliminally sensitized animals augmented the DH response while inhibiting the subliminal DH response when administered ...
TL;DR: The data suggest prophylactic treatment with IL-2 for drug induced immunosuppression is feasible and that pretreatment of effector cells for one hour with rIL-2 yieldseffector cells which are more resistant to drug-induced immunOSuppression.
Abstract: This study investigated whether in vitro immunotherapy with rIL-2 which augments human natural cytotoxicity and generation of lymphokine-activated killer cells diminished or inhibits the severity of therapeutically induced human in vitro NK immunosuppression. We demonstrate that rIL-2 induces a rapid and potent enhancement of cytolytic killing and that pretreatment of effecter cells for one hour with rIL-2 yields effecter cells which are more resistant to drug-induced immunosuppression. Additionally, we demonstrate cells pretreated for 24 hours with rIL-2 were less sensitive to drug inhibitory effects than rIL-2 non-treated or one hour pretreated effecter cells. Our data suggest prophylactic treatment with IL-2 for drug induced immunosuppression is feasible.
TL;DR: Peritoneal exudate cells collected from mice 7 days after treatment with Bordetella pertussis vaccine exhibited significant in vitro antiviral activity against vesicular stomatitis virus (VSV).
Abstract: Peritoneal exudate cells collected from mice 7 days after treatment with Bordetella pertussis vaccine exhibited significant in vitro antiviral activity against vesicular stomatitis virus (VSV). Vaccine-induced peritoneal exudate cells exhibited both intrinsic and extrinsic antiviral activity in culture with target VSV-infected L cells. Virus replication was poor in the vaccine-induced exudate cells. Coculture of vaccine-induced exudate cells and VSV-infected L cell targets decreased virus yield. The activity appeared specific for infected cells and at least a portion of the antiviral activity was directed against the initial infection cycle. Nonadherent vaccine-induced exudate cells showed an increase in antiviral activity over total vaccine-induced exudate cells.