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S Beissert

Publications and source records attributed to S Beissert.

At least 37 records · Page 2Linked to original sources
PubMed1998

Psoriasis vulgaris treated successfully with mycophenolate mofetil.

Mycophenolate mofetil (MMF) is a new immunosuppressive drug which non-competitively and reversibly blocks the de novo synthesis of guanine nucleotides required for DNA and RNA synthesis during T- and B-cell proliferation. This induces a selective inhibition of lymphocyte proliferation. Thus MMF is currently used to prolong graft survival in renal transplant patients. In this communication we describe the first case of a man with severe psoriasis treated successfully with oral MMF without short-term side-effects. The psoriasis area and severity index score decreased during therapy (5 weeks) from 22.0 to 11.4. Thus MMF appears to be an effective therapeutic alternative in the treatment of severe psoriasis.

Aged↗
PubMed1998

Differential regulation of epidermal cell tumor-antigen presentation by IL-1alpha and IL-1beta.

IL-1 exists in two forms, termed IL-1alpha and IL-1beta, which exert similar effects in a number of biologic models. Recently, there have been reports of some differences in the activities of these two species in some systems. To address this issue with regard to Langerhans cells, Langerhans cell-enriched preparations of epidermal cells were treated with either IL-1alpha or IL-1beta before pulsing with S1509a tumor-associated antigens and subsequent use for immunization of naive mice to S1509a. While epidermal cells treated with 100 U IL-1beta per ml were able to induce protective tumor immunity (as indicated by the rejection of a subsequent tumor challenge with viable S1509a tumor cells), epidermal cells treated with 100 U IL-1alpha per ml failed to confer protective immunity. At 1000 U per ml, IL-1beta also inhibited the ability of epidermal cells to induce tumor immunity. To investigate the effects of the two IL-1 forms on elicitation of tumor immunity, naive mice were immunized against the S1509a tumor by s.c. injection of dead S1509a cells. Epidermal cells enriched for Langerhans cells were treated with either 100 U IL-1alpha or IL-1beta per ml before tumor-associated antigens-pulsing. Epidermal cells were then washed and injected into a hind footpad of tumor immune mice and 24 h footpad swelling was assessed as a measure of delayed-type hypersensitivity. Exposure to IL-1alpha led to suppressed elicitation of delayed-type hypersensitivity, whereas IL-1beta treated epidermal cells elicited a normal (100 U per ml) or enhanced (1000 U per ml) level of delayed-type hypersensitivity. Previous experiments indicated that the suppressive effects of IL-1alpha on induction of immunity may be mediated by TNF alpha. Therefore, the ability of IL-1alpha or IL-1beta to induce epidermal cell production of TNF alpha was assessed. IL-1alpha induced epidermal cells to secrete significantly higher amounts of TNF alpha protein compared with stimulation with IL-1beta. IL-1alpha and IL-1beta appear to differentially regulate epidermal cell antigen presenting capability.

Animals↗
PubMed1997

Regulation of tumor antigen presentation by urocanic acid.

Urocanic acid (UCA) accumulates in the epidermis after deamination of histidine. UCA isomerizes from the trans to the cis form upon exposure to environmental UV radiation. Cis-UCA is immunosuppressive in several models. Topically applied cis-UCA was reported to enhance the cutaneous tumor yield in chronically UV-irradiated mice, suggesting involvement of cis-UCA in photocarcinogenesis. Since Langerhans cells (LC) are capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor-immune responses, we examined the effects of trans- and cis-UCA on LC tumor Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2a). In this system, induction of immunity requires exposure of LC to granulocyte-macrophage CSF. Naive CAF1 (H-2(a/d)) mice were immunized against S1509a by injection with granulocyte-macrophage CSF-exposed and TAA-pulsed epidermal cells (EC), as assessed by growth inhibition of inoculated tumor cells. Incubation of EC in cis-, but not trans-UCA completely inhibited Ag presentation in this system. Neither histamine antagonists nor indomethacin reversed these effects of cis-UCA. The ability of trans- and cis-UCA to modulate EC presentation of TAA for secondary immune responses was also examined. EC were pulsed with TAA in vitro and then injected into hind footpads of tumor-immune mice. After 24 h, footpad swelling was assessed as a measure of delayed-type hypersensitivity. Incubation with cis-, but again not trans-UCA before TAA exposure significantly inhibited elicitation of delayed-type hypersensitivity. These data indicate that cis-UCA may be an important regulator of LC Ag-presenting function in tumor-immune responses, and thus may play a role in photocarcinogenesis.

Animals↗
PubMed1997

Regulation of cytokine expression in macrophages and the Langerhans cell-like line XS52 by calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP) inhibits antigen presentation by Langerhans cells (LC) and macrophages, and LC are anatomically associated with CGRP-containing epidermal nerves. To determine whether CGRP may produce some of its functional effects through regulation of cytokine expression, we utilized enzyme-linked immunosorbent assay (ELISA) of conditioned supernatants to examine production of interleukin (IL)-10 and IL-1 beta protein in the LC-like cell line XS52 as well as the reverse transcriptase-polymerase chain reaction (RT-PCR) to examine levels of mRNA for IL-10, IL-1 beta, and the 40-kDa subunit (p40) of IL-12. CGRP augmented the lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) -induced release of IL-10 protein and the induced expression of IL-10 mRNA in these cells. However, it suppressed the induction of release of IL-1 beta protein and the induction of mRNA for IL-12 p40 and IL-1 beta by LPS and GM-CSF. Regulation of cytokine expression in peritoneal macrophages was also examined. By ELISA, the LPS-induced expression of IL-10 was augmented by CGRP, whereas the induction of IL-1 beta was suppressed. Northern analysis demonstrated augmentation of LPS-induced IL-10 mRNA levels and inhibition of LPS-induced IL-1 beta mRNA by CGRP. CGRP inhibited the LPS-induced induction of IL-12 mRNA as assessed by RT-PCR. Up-regulation of B7-2 expression by LPS and GM-CSF was suppressed by CGRP in both XS52 cells and macrophages, as previously reported. This suppression, however, could be abrogated by co-culture with neutralizing antibodies to IL-10. Furthermore, the presence of neutralizing antibodies to IL-10 during exposure of epidermal cells (EC) to CGRP prevented the CGRP-mediated suppression of EC presentation of tumor-associated antigens (from the S1509a spindle cell carcinoma) for elicitation of delayed-type hypersensitivity in S1509a-immune mice. These data suggest that suppression of antigen-presenting function by CGRP is mediated, at least in part, by changes in cytokine expression that favor less robust antigen presentation for cell-mediated immunity.

Animals↗
PubMed1996

Inhibition of neutrophil elastase suppresses the development of skin tumors in hairless mice.

In this study we investigated whether a reduction in neutrophil elastase activity in mice would alter the development of ultraviolet B or chemically induced skin tumors. A mutant strain of neutrophil elastase-deficient mice was developed by crossing beige mice with SKH 1 hairless mice. Ultraviolet irradiation three times per week for 20 wk developed an average of 10 tumors per normal mouse, whereas elastase-deficient hairless mice receiving the same treatment developed only 0.4 tumors per mouse. Benzopyrene administered topically for 20 wk resulted in an average of seven tumors per control mouse, while similar treatment to elastase-deficient hairless mice reduced the tumor count to 0.2 per mouse. Two small molecular weight elastase inhibitors, which were shown to inhibit mouse neutrophil elastase, were administered subcutaneously to normal SKH-1 mice during 16 wk of ultraviolet B exposure. Both inhibitors significantly reduced the incidence of ultraviolet B-induced tumors. When control and elastase-deficient mice were immunized with 2,4,6-trinitrochlorobenzene and oxazolone, both molecules elicited a significant contact hypersensitivity response. Ultraviolet B irradiation prior to immunization at a nonirradiated site completely suppressed the induction of contact hypersensitivity in both the normal and the deficient mice, suggesting that prevention of systemic immunosuppression was not the reason for the resistance to skin tumors observed in the elastase-deficient mice. The results suggest that neutrophil elastase can be an important factor in squamous cell tumor development.

Animals↗
PubMed1996

Hyporesponsiveness in contact hypersensitivity and irritant contact dermatitis in CD4 gene targeted mouse.

To determine the role of CD4 molecules in the generation and regulation of contact hypersensitivity (CHS), we treated mice lacking the CD4 gene as a result of targeted disruption with dinitrofluorobenzene to induce CHS. The mutant mice lacking CD4 (CD4(-) mice) showed marked hyporesponsiveness in CHS compared with normal syngeneic C57BL/6 mice (38.3 +/-9.0% of normal at 24 h after the challenge assessed by net ear swelling; p < 0.025). CD4(-) mice had a larger CD4-8- double negative T-cell receptor alpha beta+ cell population in the lymph nodes than did normal mice, and the increase of this cell population was observed in CD4(-) mice after sensitization. Draining lymph node cells from sensitized normal mice restored the responsiveness in CD4(-) mice, but those from sensitized CD4(-) mice were less effective in restoring the CHS response in normal mice. Langerhans cell numbers were normal, and function, as assessed by the ability to present soluble hapten, was not impaired in CD4(-) mice. Skin cytokine profiles demonstrated an increase in interferon-gamma, interleukin-2, and interleukin-4 mRNA levels after challenge in normal mice, whereas this response was blunted in CD4(-) mice. CD4(-) mice also showed hyporesponsiveness in inflammatory reaction to irritant chemicals. These results suggest that the CD4 molecule is required for optimal induction of CHS as well as irritant contact dermatitis and may influence the development of CHS by modulating the cytokine profiles in the skin.

Animals↗
PubMed1996

Impaired immunosuppressive response to ultraviolet radiation in interleukin-10-deficient mice.

Exposure to mid-range ultraviolet radiation (UVR) [280-320 nm, ultraviolet B (UVB) radiation] inhibits the acquisition of delayed-type hypersensitivity in mice and contact hypersensitivity in rodents and humans. Intraperitoneal administration of interleukin 10 (IL-10) inhibits the sensitization of mice to alloantigens for a delayed-type hypersensitivity reaction and administration of neutralizing antibodies to IL-10 largely, but not totally, blocks the UVR-mediated suppression of the ability to sensitize mice. This suggests that these inhibitory effects of UVB radiation may be mediated by release of IL-10. To test this hypothesis directly, IL-10 gene-targeted (IL-10T) mice lacking expression of IL-10 were examined for the ability of UVB radiation to suppress induction of delayed-type hypersensitivity to alloantigens. IL-10T mice were completely resistant to UVB-induced immunosuppression in this system. Interestingly, UVB radiation could suppress in IL-10T mice the induction of contact hypersensitivity to a hapten applied to the skin at a site distant of irradiation, supporting the concept that regulation pathways of delayed-type hypersensitivity and contact hypersensitivity responses by UVR differ. These data provide additional understanding of the mechanisms of immunosuppression induced by UVR and suggest that IL-10 release subsequent to UVB radiation may play a role in the growth immunogenic UVB-induced cutaneous malignancies in the primary host.

Animals↗
PubMed1996

UV-induced cutaneous photobiology.

Ultraviolet radiation (UVR) present in sunlight is a major environmental factor capable of affecting human health and well being. The organ primarily affected by UVR is the skin, which is composed of a variety of different cell types. Here, UVR is needed for production of active vitamin D as well as producing undesirable effects such as sunburn, premature cutaneous photoaging, and promoting skin cancer development. Depending on the radiation dose, UVR influences virtually every cutaneous cell type investigated differently. Since the end of the nineteenth century, sun exposure has been known to induce skin cancer, which is now the human malignancy with the most rapidly increasing incidence. In several experimental models, mid-range UVR has been demonstrated to be the major cause of UV-induced cutaneous tumors. The stratospheric ozone layer protecting the terrestrial surface from higher quantum energy solar radiation is being damaged by industrial activities resulting in the possibility of increased UVR exposure in the future. Investigations in the field of experimental dermatology have shown that within the skin an immunosurveillance system exists that may be able to detect incipient neoplasms and to elicit a host responses against it. This article reviews the literature on studies designed to investigate the effects of UVR on cutaneous cellular components, with special focus on the immune system within the skin and the development of UV-induced cancer.

Apoptosis↗
PubMed1995

Inhibition of the induction of delayed-type and contact hypersensitivity by calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP)-containing nerves are frequently associated anatomically with epidermal Langerhans cells (LC), and LC Ag-presenting function is down-regulated by CGRP. To investigate possible regulation of cutaneous immunity by CGRP, we examined its effect on the induction of delayed-type hypersensitivity (DTH) and contact hypersensitivity (CHS). A system of immunity to the murine spindle cell tumor S1509a (H-2a) was employed to examine induction of DTH by LC. This system requires exposure of epidermal cells (EC) to GM-CSF for induction of substantial immunity. EC were prepared from CAF1 mice (H-2a/d) and Thy-1+ cells deleted. EC were exposed for 16 h to GM-CSF with or without CGRP. EC were then pulsed with tumor-associated Ags (TAA), washed, and injected s.c. into mice three times at 7-day intervals for immunization. Mice were challenged for a DTH response by injection of a hind footpad with TAA-pulsed EC, and 24-h footpad swelling assessed. Exposure of EC to CGRP significantly inhibited induction of DTH. To examine the effect of CGRP administered in vivo on induction of immunity, 530 pmol of CGRP or diluent alone was injected intradermally into the dorsum of the left ear of naive mice 8 h and 3 h before epicutaneous application of a hapten at the injected site. Mice were challenged on the right ear 7 days later and 24 h ear swelling was assessed. CGRP significantly inhibited the induction of CHS whereas calcitonin had no effect. Furthermore, when hapten was applied at a site distant from CGRP administration, no inhibition of CHS was observed, suggesting that the effect of CGRP is local. These data support the concept that CGRP may be an endogenous regulator of immune function and also suggest the possibility that CGRP or its analogues administered in vivo might have therapeutic utility as immunomodulators.

Animals↗
PubMed1995

IL-10 inhibits tumor antigen presentation by epidermal antigen-presenting cells.

IL-10 inhibits Langerhans cell (LC) Ag presentation to Th1 clones. As LC are capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor immune responses, we examined the effect of IL-10 on LC Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2a). Because induction of immunity to S1509a requires exposure of LC to granulocyte-macrophage (GM)-CSF, this system also allowed us to study the regulatory interactions of GM-CSF and IL-10 on LC. Naive CAF1 (H-2a/d) mice could be immunized against S1509a by injection with GM-CSF-exposed and TAA-pulsed epidermal cells (EC) as assessed by inhibition of the growth of inoculated tumor cells. Incubation of EC in IL-10 before GM-CSF exposure completely inhibited Ag presentation in this system. Significantly, neither co-incubation of EC in IL-10 and GM-CSF (without preincubation in IL-10) nor IL-10 treatment after GM-CSF incubation was able to exert a down-regulatory effect. The ability of IL-10 to modulate EC presentation of TAA for a secondary immune response was also examined. EC were pulsed with TAA in vitro and then injected into a hind footpad of tumor-immune mice with 24 h swelling assessed as a measure of delayed-type hypersensitivity. Preincubation in IL-10 before TAA exposure significantly inhibited elicitation of delayed-type hypersensitivity with or without subsequent exposure to GM-CSF. Co-incubation of EC in IL-10 and GM-CSF or exposure to IL-10 after GM-CSF led to a normal response. These data indicate that IL-10 may serve as an important regulator of LC Ag-presenting function for tumor immune responses. IL-10 appears to specifically prevent the GM-CSF-induced maturation of LC Ag-presenting function when treatment with IL-10 occurs before exposure to GM-CSF but does not reverse the established mature state.

Animals↗
PubMed1995

Supernatants from UVB radiation-exposed keratinocytes inhibit Langerhans cell presentation of tumor-associated antigens via IL-10 content.

Exposure of mice to midrange UV radiation (UVB) (280-320 mm) in vivo leads to suppression of the ability to induce delayed-type hypersensitivity (DTH). Systemic administration of supernatants from UVB-exposed keratinocytes (KC) similarly inhibits the ability to induce DTH and the presence of interleukin-10 (IL-10) in the supernatants has been shown to be responsible for this effect. It has been hypothesized that release of IL-10 by KC after exposure to UVB radiation in vivo may be responsible for UVB-induced inhibition of DTH and also for the inability of chronically UVB-irradiated mice to immunologically reject immunogenic UVB-induced skin tumors. To test directly whether supernatants from UVB-irradiated KC can inhibit presentation of tumor-associated antigens (TAA) by epidermal Langerhans cells (LC), cultures of the transformed murine KC line PAM 212 were exposed to 200 J/m2 of UVB radiation and 24 h supernatants obtained. CAF1 (H-2a/d) epidermal cells (EC) enriched for LC content were exposed to supernatants from irradiated (UV-SN) or mock-irradiated (MI-SN) PAM 212 cells for 3 h followed by culture for 16 h in granulocyte-macrophage colony-stimulating factor and then were pulsed with soluble TAA derived from the murine spindle cell tumor S1509a (H-2a). ECs were then washed and injected subcutaneously into naive CAF1 mice three times at weekly intervals for priming. One week after the final immunization these mice were challenged subcutaneously with live S1509a cells and tumor growth scored over time. Pretreatment of EC with UV-SN but not MI-SN inhibited the induction of effective immunity by this immunization scheme. ECs were also treated with UV-SN or MI-SN for 3 h then pulsed with TAA and injected into a hind footpad of previously immunized mice for elicitation of a DTH response. Pretreatment of EC with UV-SN but not MI-SN inhibited the ability of EC to elicit DTH. Neutralization studies with specific neutralizing antibodies to IL-10 demonstrated that the presence of IL-10 in UV-SN was responsible for the inhibition of antigen presentation both for induction and elicitation of immunity. UV-SN inhibits tumor antigen presentation by epidermal LC through the action of IL-10.

Animals↗
PubMed1994

Interferon-gamma inhibits tumor antigen presentation by epidermal antigen-presenting cells.

Murine I-A+ epidermal antigen-presenting cells (APCs) have been shown to be capable of presenting soluble tumor fragments (TFs), as a source of tumor-associated antigens (TAAs), for primary and secondary tumor immune responses. In this study we investigated whether incubation of epidermal APCs in interferon-gamma (IFN-gamma) modulates their ability to present TAA and whether the effects of IFN-gamma on the presentation of tumor antigen correspond to its effects on alloantigen presentation in both primed and unprimed systems. Our results show that three weekly subcutaneous injections of naive mice with GM-CSF-cultured but not with fresh TAA-pulsed epidermal APCs induce protective tumor immunity in naive mice and that the immunostimulatory effect of GM-CSF in this system is abrogated by coculture of epidermal cells in IFN-gamma. Furthermore, epidermal APCs are able to present TAA to primed, tumor-immune mice, as assessed by the elicitation of tumor-specific delayed-type hypersensitivity after injection of TAA-pulsed epidermal APCs. IFN-gamma was found to inhibit tumor antigen presentation by freshly prepared epidermal APCs in this system. The effects of IFN-gamma on the presentation of tumor antigen correlated well with its effects on the primary and secondary mixed epidermal cell-lymphocyte reaction, indicating that IFN-gamma differentially modulates the function of epidermal APCs with regard to induction versus elicitation of immunity.

Animals↗
PubMed1993

[Pemphigus herpetiformis].

Pemphigus herpetiformis is an unusual variant of pemphigus. Clinically it can resemble Duhring's disease, while histopathological examination and, in particular immunofluorescence yield findings diagnostic for pemphigus. As pemphigus herpetiformis responds quite well to sulfones, recognition of this rare disorder is of practical relevance. In the present report, a case of pemphigus herpetiformis with an unusually young age of onset is presented. In addition, clinical features, results of histopathological examination and immunofluorescence, differential diagnosis and treatment are discussed.

Adult↗
PubMed1992

Heterogeneity of tumour necrosis factor production in renal cell carcinoma.

Endogenous tumour necrosis factor (TNF) production was investigated by in situ hybridisation and immunohistochemistry in 8 renal cell carcinoma (RCC) patients at different stages of disease. Analysis of frozen sections of tumour biopsy specimens revealed variable degrees of macrophage infiltration and great heterogeneity in TNF gene expression. Two metastatic tumours investigated showed abundant TNF protein production and marked macrophage infiltration. Based on morphological criteria, these TNF-positive cells most likely belong to the macrophage lineage. Two years after nephrectomy the individual survival time was recorded; however, the small numbers did not yet allow any correlation of TNF production to the clinical course of disease. Further studies will be required to eventually reveal the role of TNF in renal cell carcinoma development.

Aged↗
PubMed1989

Regulation of tumor necrosis factor gene expression in colorectal adenocarcinoma: in vivo analysis by in situ hybridization.

Tumor necrosis factor (TNF) produced by macrophages is thought to contribute to the host defense against development of cancer. However, since tumor cells themselves are able to produce TNF, it is conceivable that TNF may also play an adverse pathological role in carcinogenesis. To better understand the functional significance of TNF in neoplastic disease, we have determined the cellular source of TNF activity produced in 10 patients with colorectal cancer. Northern blot analysis of RNAs extracted from fresh biopsy specimens revealed detectable TNF mRNA levels in all instances. By using in situ hybridization of frozen sections, scattered cells expressing TNF mRNA could be discerned. Based on morphological criteria, these TNF-positive cells most likely belong to the macrophage lineage. Macrophages in normal tissue surrounding the tumor did not express TNF mRNA, suggesting that macrophage activation occurs locally at the site of neoplastic transformation. Immunohistochemistry using anti-TNF monoclonal antibodies revealed that less than 1% of tumor-infiltrating macrophages synthesize TNF protein. Thus we present evidence that in colorectal cancer only a small proportion of tumor-infiltrating macrophages produces TNF, indicating that the microenvironment of the tumor provides adequate, yet suboptimal, conditions for macrophage activation.

Adenocarcinoma↗