RESUMEN

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is an important cytokine in the early stage of systemic sclerosis (SSc), which is characterized by mononuclear cell infiltration and microvascular alterations. Most effects of TNF-alpha are mediated by its interaction with 2 types of TNF receptors and depend on their surface expression on individual cell subsets. Our purpose was to correlate the serum levels of soluble TNF receptors-TNF-RI(p55) and RII(p75)-with (1) their in situ expression and distribution in lesional skin and on peripheral blood mononuclear cells (PBMC), and (2) the clinical disease progression and inflammatory serum variables in patients with SSc. METHODS: Serum samples of 32 patients with SSc and 36 healthy probands were examined by ELISA. We performed immunohistological stainings and in situ hybridization on cryostat sections of skin lesions, cytometric analysis on PBMC, and reverse transcriptase polymerase chain reactions using RNA from cultured skin fibroblasts in 17 of these 36 patients. RESULTS: In contrast to healthy skin and chronic fibrotic SSc, TNF-RI is expressed on about 30% of mononuclear infiltrating cells in early skin lesions. Neither TNF-RI nor RII was detectable on fibroblasts by immunohistochemistry, but specific mRNA could be found on the transcriptional level. TNF-RII is found on most lymphocytes and on 30-50% of endothelial cells, especially in early SSc. Expression of both receptor types on PBMC in patients and controls was not significantly different. Serum levels of soluble TNF-RI and RII correlated well with their in situ expression and with clinical and laboratory signs of inflammation and disease progression in patients with SSc. CONCLUSION: Our data provide evidence for a central role of the TNF-alpha/TNF-R system in the early pathological events of scleroderma with prominent inflammation and endothelial cell damage. Determination of TNF-R serum levels provides a useful diagnostic tool for characterization of the disease stage and progression, and to guide experimental therapy in patients with SSc.

Asunto(s)

Receptores del Factor de Necrosis Tumoral/metabolismo , Esclerodermia Sistémica/metabolismo , Adulto , Anciano , Biopsia , Células Cultivadas , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Inflamación/inmunología , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral/sangre , Receptores del Factor de Necrosis Tumoral/inmunología , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/inmunología , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/metabolismo

RESUMEN

OBJECTIVE: To investigate the expression patterns of interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), both of which are potent inducers of class II major histocompatibility complex (MHC) and intercellular adhesion molecule 1 (ICAM-1) expression, and their codistribution with HLA-DR and ICAM-1 in skin lesions, cultured fibroblasts, and peripheral blood mononuclear cells (PBMC) of systemic sclerosis (SSc) patients in different stages of disease. METHODS: Investigations were carried out using immunohistochemistry studies, reverse transcriptase-polymerase chain reaction, dot-blot hybridization, and cytometric analysis. Serum levels of TNF alpha were determined by enzyme-linked immunosorbent assay. RESULTS: In the early inflammatory stage of SSc, class II MHC and ICAM-1 expression could be detected on most endothelial cells and on fibroblasts located especially in perivascular areas surrounded by infiltrating lymphocytes, which belong to the T helper 1 phenotype expressing IFN gamma and TNF alpha. In this early disease stage, an enhanced expression of TNF alpha on cultured dermal fibroblasts and PBMC, as well as elevated serum titers of soluble TNF alpha, could be found. CONCLUSION: These data suggest that class II MHC antigens and ICAM-1 on fibroblasts and endothelial cells are induced by IFN gamma and TNF alpha in an early stage of SSc after the influx of mononuclear-cells, and may be important in the putative autoimmune response and in the perpetuation of fibrotic processes in SSc.

Asunto(s)

Antígenos de Histocompatibilidad Clase II/fisiología , Molécula 1 de Adhesión Intercelular/biosíntesis , Interferón gamma/farmacología , Esclerodermia Sistémica/patología , Esclerodermia Sistémica/fisiopatología , Factor de Necrosis Tumoral alfa/farmacología , Adulto , Anciano , Enfermedad Crónica , Técnicas Citológicas , Endotelio/citología , Endotelio/efectos de los fármacos , Endotelio/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Esclerodermia Sistémica/inmunología , Piel/química , Piel/inmunología , Piel/patología , Regulación hacia Arriba/efectos de los fármacos

Asunto(s)

Fluorescencia , Tecnología Radiológica , Tungsteno , Calcio , Métodos , Fotograbar , Radiación

RESUMEN

Two glass filters for the sensitometric exposure of daylight films are described. The filters are each made of four glass color filters. The thickness of the four glasses is chosen to match two types of relative energy distributions of sensitometric daylight with a tungsten lamp operated at 2850 degrees K. The differences of the relative spectral transmittance of the glass filter sets compared with corresponding two chamber solution Davis-Gibson filters are so small that no essential changes of the characteristic curves of several black and white and color films have been observed in a group of experiments.