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Biomedical subjects

H Kirchner

Publications and source records attributed to H Kirchner.

At least 307 records · Page 17Linked to original sources
PubMed1987

Induction of interferon-gamma in human leukocyte cultures stimulated by Zn2+.

Our studies have confirmed previous reports that Zn2+ has a mitogenic effect on human lymphocytes. Furthermore, we have tested the ability of Zn2+ to induce interferon production in human leukocyte cultures. Peripheral blood mononuclear cells were stimulated with ZnCl2 at different concentrations. Interferon was detected in the supernatants of cultures stimulated with concentrations ranging from 5 X 10(-4) to 5 X 10(-5) M. Interferon was produced only in the presence of accessory cells. The type of interferon induced by Zn2+ was interferon-gamma, as proven by the use of specific antisera.

Cells, Cultured↗
PubMed1987

Measurement of cell-mediated immunity against bovine papilloma virus by lymphoproliferative reactions.

To study cellular immunity towards bovine papillomavirus (BPV), calves were infected intradermally with BPV-1, and the cellular immune response was measured by the lymphocyte proliferation assay. Peripheral blood lymphocytes were obtained which in control experiments were highly reactive towards mitogen stimulation. Different batches of BPV-1 were prepared by the use of density gradients. In the first set of experiments, a nonspecific mitogenic effect of the virus preparation was observed. This effect was obviously caused by soluble molecules contained in the virion-free supernatant obtained after ultracentrifugation of the viruses. Subsequently, we obtained highly purified virions which did not share the nonspecific mitogenic effect. The data obtained with these virions showed no responses of untreated control animals but a short-lived in vitro lymphoproliferative response 2 to 3 weeks after infection. This response then disappeared and was followed by a period of non-responsiveness which lasted as long as we tested the animals.

Animals↗
PubMed1987

The role of gamma interferon in B-cell activation.

This study evaluates the role of gamma interferon in in vitro B-cell activation. Two clones of an alloreactive helper T-cell line were equally effective in activating B cells polyclonally to proliferate and to mature to immunoglobulin secretion. One of these clones produced high levels of gamma interferon, while the other clone did not. From these data we conclude that gamma interferon plays no limiting role in T-dependent B-cell activation.

Animals↗
PubMed1987

Reduced production of interferon alpha and interferon gamma in leukocyte cultures from patients with active rheumatoid arthritis.

Tests for lymphoproliferation and interferon induction in normal blood donors and patients with rheumatoid arthritis (RA) were performed in a whole-blood assay. Patients with high inflammatory RA showed significantly reduced lymphoproliferation and interferon gamma production after stimulation with phytohemagglutinin (PHA) and concanavalin A (Con A) when compared with patients with low inflammatory activity, or with normal control individuals. Similarly, patients with high and low inflammatory RA exhibited a significantly reduced interferon alpha production after stimulation with Newcastle Disease Virus (NDV) when compared with normal blood donors. Our findings may point to an important immunodeficiency of the circulating lymphocytes of RA patients and may explain some of the in vitro immunoregulatory abnormalities reported in this disease.

Arthritis, Rheumatoid↗
PubMed1986

Synthesis of herpes simplex virus proteins and nucleic acids in interferon-treated macrophages.

Mouse macrophages grown from spleen cells were found to be very sensitive to the interferon (IFN) activity against herpes simplex virus type 1 (HSV-1). Therefore we have used these cells to investigate the level at which IFN blocks the replication of HSV-1. IFN treatment resulted in a strong inhibition of the induction of HSV DNA polymerase and other beta proteins. RNA hybridization experiments revealed that the amount of mRNA for the beta protein thymidine kinase was strongly reduced in IFN treated HSV-1 infected cells. Analysis of the effect of IFN on expression of the alpha genes indicated a strong inhibition of alpha protein synthesis. In contrast the synthesis of mRNA of the alpha protein ICP 4 was only moderately inhibited. The results indicate that IFN primarily acts on the translation of HSV alpha proteins.

Animals↗
PubMed1986

Activation of murine B lymphocytes by suramin.

Suramin stimulated DNA synthesis in spleen cell cultures of all inbred strains of mice tested, including, for example, CBA, DBA/2, C57BL/6, and the lipopolysaccharide (LPS)-nonresponsive strain C3H/HeJ. The cells responding to the drugs were removed by passage through nylon wool columns, but they were not eliminated by in vivo treatment of the mice with anti-Thy 1.2 antibody. Spleen cells of homozygous nude mice (C57BL/6 or BALB/c background) were as reactive as those of their heterozygous littermates. Collectively the data show that suramin is a B-cell mitogen in the mouse.

Animals↗
PubMed1986

T lymphocytes activated by interleukin 2 alone acquire permissiveness for replication of herpes simplex virus.

Not only mitogen stimulation or mitogen stimulation in combination with interleukin 2 (IL2) was capable of causing susceptibility of human T lymphocytes to herpes simplex virus (HSV) infection, but also selective stimulation with recombinant Il2-induced permissiveness of T lymphocytes to HSV infection. Replication of HSV in such IL2-stimulated T cell cultures was shown to be restricted to a T cell subset not exceeding 5% of the total population. Furthermore, IL2 stimulation was sufficient to obtain virus replication in T cells previously infected by HSV and cultivated for several days. This could not be achieved by stimulation with mitogens such as phytohemagglutinin. The level at which virus replication was restricted in nonpermissive T cells was determined to be before immediate early gene expression as assessed by indirect immunofluorescence with monoclonal antibodies against viral proteins expressed at different stages of the viral replicative cycle.

Cell Transformation, Viral↗
PubMed1986

Prolongation of survival of mice bearing the Eb and ESb lymphoma by treatment with interferon inducers alone or in combination with Corynebacterium parvum.

The objective of this study was to evaluate if pretreatment with Corynebacterium parvum (C. parvum) augments the effects of interferon (IFN) inducers on survival of DBA/2 mice transplanted with two syngeneic lymphoma variants, the low metastatic Eb and the high metastatic ESb tumor. The involvement of IFN in the treatment effects was investigated. As inducers of IFN-alpha/beta Newcastle disease virus (NDV), polyinosinic-polycytidylic acid (polyI:polyC), and 10-carboxymethyl-9-acridanone (CMA) were injected i.p. at the site of tumor transplantation. The Eb tumor was found to be sensitive to the antiproliferative action of IFN-alpha/beta in vitro. In vivo single injections of each of the inducers retarded growth of the Eb tumor. In C. parvum-pretreated mice the effects of the inducers on survival were markedly increased. There was a correlation between prolonged survival and local IFN levels in response to polyI:polyC or CMA but not upon NDV. Injections of each of the inducers increased cytotoxicity of peritoneal exudate cells against the Eb tumor cells in vitro especially when mice were pretreated with C. parvum. Although other mechanisms cannot be excluded IFN-mediated activation of host defence and also direct antiproliferative effects of endogenously produced IFN seem to be involved in the antitumor effects by these IFN inducers in the Eb model. In the ESb tumor model irrespective of additional pretreatment with C. parvum survival was only slightly prolonged by the treatments and endogenous IFN induction did not result in any real benefit for the animals. When compared with Eb cells the ESb cells were less sensitive to the antiproliferative action of IFN-alpha/beta in vitro and less sensitive to in vitro cytotoxicity by the host cells. Although other mechanisms may additionally be active in vivo the different susceptibility of the Eb and ESb tumor cells to the direct and indirect actions of IFN seems to contribute to the different responsiveness of these tumor cell lines to the treatments with IFN inducers.

Acridines↗
PubMed1986

Effect of interleukin-2 on the manifestation and growth of acetoxymethyl-methylnitrosamine-induced colorectal rat adenocarcinoma.

The effect of highly purified human interleukin-2 (IL-2) was assessed on acetoxymethyl-methylnitrosamine(AMMN)-induced colorectal Sprague-Dawley rat adenocarcinoma. Treatment was given for 5 weeks and started 5 weeks after a period of 10 weeks intrarectal administration of 2 mg/kg of AMMN once a week. Animals which showed no evidence of tumors by endoscopical examination of the gut were given 10,000 units/kg of IL-2 s.c. into the dorsal region 5 days a week. Blood samples were analyzed from half of the animals before and 72 h after the end of the treatment. The median tumor volume and the median tumor number per rat were lower in the treated group than in the control. A significant decrease in response to two mitogens (PHA, Con-A) was seen in tumor-bearing rats concomitantly with the tumor growth. The immunological suppression was not restored by treatment with IL-2. No differences in natural killer activity or interferon levels were detected between the control and the treated group. These data indicate some antitumor effect of IL-2 given before the manifestation of tumors in AMMN-induced colorectal rat adenocarcinoma.

Adenocarcinoma↗
PubMed1986

Modulation of granulocyte oxidative response by recombinant interferon alpha 2 and gamma.

Interferon (IFN) has been described to influence various cellular functions. In this study we investigated whether the oxidative response of polymorphonuclear leukocytes (PMN) is also affected by IFN. In order to exclude the possible influence of impurities in IFN preparations, only recombinant human IFN alpha 2 or gamma were used. Lucigenin-dependent chemiluminescence (CL) of PMN was measured to assess the production of oxygen radicals. IFN gamma at a concentration of more than 10 ng/ml elicited a minimal CL response in PMN. When PMN were incubated with IFN gamma for 1 h and then stimulated with chemotactic peptide f-met-phe (FMP), zymosan-activated serum (ZAS), zymosan particles, or phorbol-myristate acetate (PMA), the CL response was increased as consequence of the generally enhanced oxidative metabolism. IFN alpha 2 showed no such effect at any concentration tested. A 5-min pretreatment with IFN gamma decreased the ZAS response but did not affect the reaction to the other stimuli. The possibility of a generation of IFN by PMN during the assay could be excluded as no IFN activity could be detected in an antiviral assay after stimulation of PMN for 6 h with PolyI X PolyC, LPS, ConA, C. parvum, PMA, zymosan, or FMP. The modulation of granulocyte activity by IFN gamma may be important in the regulation of the anti-inflammatory response of PMN.

Acridines↗
PubMed1986

Depression of cellular immunity after open-heart surgery.

Using a whole blood test system we investigated cell-mediated immunity in 45 patients undergoing open-heart surgery. The peripheral blood lymphocytes were stimulated with the nonspecific mitogens phytohemagglutinin, concanavalin A and pokeweed mitogen, one bacterial recall antigen, tuberculin PPD, and one viral antigen, herpes simplex virus. The patients were tested three times: pre-operatively, and seven days and 2 wks post-operatively. There were no significant differences between a control group of healthy blood donors and the patient group tested preoperatively. However, seven days after operation we observed a clear decrease of the reactions to all stimulants. Two weeks after operation there was an increase of lymphocyte proliferation data in regard to tuberculin PPD and herpes simplex virus. Concerning the nonspecific mitogens PHA and PWM, there was only a tendency of an increase. We believe that two weeks after operation is too short an interval to notice a full normalization of the cellular immune functions. In comparison with the conventional system of isolated lymphocytes, the whole blood technique is advantageous in investigating cell-mediated immunity, particularly if the patient groups are large.

Adult↗
PubMed1986

Effects of cyclosporin A on functions of specific murine T cell clones: inhibition of proliferation, lymphokine secretion and cytotoxicity.

Allospecific T lymphocyte clones with different functions were generated from spleen cells of C 57/Bl6 mice following sensitization in vitro by a one-way mixed lymphocyte culture (MLC) with irradiated DBA/2 spleen cells. The clones were propagated in vitro in the presence of interleukin 2 (IL 2) and restimulation with stimulator cells. In these clones Cyclosporin A (CSA) was tested for its suppressive effect on different T lymphocyte functions. The antigen-dependent proliferation of a helper clone (HTL) was totally inhibited by 50 ng/ml CSA. Proliferation induced by simultaneous administration of antigen and IL 2 was partially suppressed in all helper and cytotoxic clones (CTL). The IL 2-driven proliferation in the absence of antigen was also suppressed between 25-70% by the immunosuppressive drug. Secretion of macrophage activating factor (MAF) and interferon (IFN) by HTL and CTL in response to antigen or mitogen was reduced dose dependently by CSA. Concentrations of 50 ng/ml CSA diminished lymphokine secretion to approximately 10% of controls, also when excess IL 2 was present. Cytotoxicity, previously described to be insensitive to the drug, could be suppressed by 50 ng/ml CSA to a various extent, from 40-70%, in different cytotoxic clones when the effector cells were preincubated with CSA for 1 h or more. Conclusively, the data suggest that CSA interferes generally with the activation of T lymphocyte clones.

Animals↗
PubMed1986

Activation of C57BL/6 spleen cells by the mitogenic principle derived from mycoplasma arthritidis.

A T cell mitogen derived from the supernatant of cultured mycoplasma arthritidis (MAS) has been recently discovered. Here we show that among a variety of strains, mycoplasma arthritidis was the only one elaborating the mitogen. Pools of MAS obtained at different occasions were quite variable in their biologic activity. Thus, in an attempt to obtain a more uniform preparation, MAS was semi-purified by Sephadex G-150 columns. Biologic activity eluted in a single peak in the molecular weight range of 13,000 daltons. "Nonresponsive" C57BL/6 spleen cells could be reconstituted to respond to MAS by the addition of 2-mercaptoethanol (2-ME). This reconstitutive effect was seen even when 2-ME was added 12 h after MAS. In further experiments, the lymphocyte culture technique was modified. Adherent spleen cells (AC) were grown and repeatedly washed before the simultaneous addition of nylon-purified T cells and MAS. Also in this experimental set-up, 2-ME could be added after the T cells. Finally, AC were cultured in the presence of MAS and after 4 h washed repeatedly. Subsequently, T cells and 2-ME were added. Also under these conditions, C57BL/6 spleen cells were capable of responding to MAS. These data suggest that 2-ME does not act on AC but on T cells. However, nylon-purified T cells in the complete absence of AC did not respond to MAS even in the presence of 2-ME. Thus, in order for the response to MAS to occur in "nonresponsive" C57BL/6 spleen cells, both AC and 2-ME are required. So far, our experiments have failed to conclusively unravel the mode of action of 2-ME. Yet, experiments using monoclonal antibodies against I-E have suggested that the response of "non-reacting" C57BL/6 spleen cells to MAS in the presence of 2-ME is not restricted by the molecule on the cell surface coded for by the I-E region.

Animals↗
PubMed1986

Analysis of the interferons induced in mice in vivo and in macrophages in vitro by Newcastle disease virus and by polyinosinic-polycytidylic acid.

C57BL/6 mice or pure cultures of their macrophages were inoculated with Newcastle disease virus (NDV) or poly(I).poly(C) to induce interferons (IFNs) that were separated on CH-Sepharose 4B columns. The elution profiles of different activity peaks were compared. All preparations induced in vivo showed the same pattern but the relative proportions of the IFN activities varied. In vitro poly(I).poly(C)-induced IFN showed two peaks after separation by the column, and three peaks were found when NDV-induced IFNs were separated. When IFN induced by NDV in vitro was used to determine the molecular weight, activities were observed in three molecular weight ranges. The smallest one with 18,000 daltons was neutralized by anti-IFN-alpha and represented about 7% of the total activity. The activities of molecular weights 24,000 daltons and 29,000-31,000 daltons were neutralized by anti-IFN-beta. Poly(I).poly(C)-induced IFN in vitro showed two molecular weight ranges, 26,000 daltons and 40,000 daltons, and both were neutralized by anti-IFN-beta. IFN induced in serum by NDV at 3 h had molecular weights of 18,000 daltons neutralized by anti-IFN-alpha and 26,000-30,000 daltons neutralized by anti-IFN-beta. Both IFN subtypes were represented at equal quantities. Serum IFN found in the serum after 8 h had three molecular weight ranges: 18,500-19,500 daltons neutralized by anti-IFN-alpha containing 80% of the total IFN amount, 26,000-27,000 daltons, and 38,000 daltons both neutralized by anti-IFN-beta and containing 20% of the IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗