RESUMEN
The signaling lymphocytic activation molecule SLAMF1 (CD150) is a co-stimulatory molecule that is expressed by most immune cells, including T regulatory (Treg) lymphocytes. Since different abnormalities have been reported regarding the number and function of Foxp3+ Treg cells in patients with systemic lupus erythematosus (SLE), we decided to analyze the expression and function of CD150 in these regulatory lymphocytes in this condition. We isolated peripheral blood mononuclear cells from 20 patients with SLE, and 20 healthy controls. The expression of SLAMF1 was determined by multi-parametric flow cytometry and the suppressive function of CD4+CD25+ lymphocytes, upon engagement or not of CD150 with an agonistic monoclonal antibody, was analyzed by an assay of inhibition of cell proliferation. We observed a significantly increased expression of SLAMF1 by CD3+CD4+ helper T cells and CD19+ B cells in patients with SLE and active disease. However, similar levels of SLAMF1 expression were detected in Foxp3+ Treg cells from patients and controls. In contrast, a higher proportion of SLE patients increased their suppressive function of Treg cells upon CD150 engagement compared to healthy controls. Our data suggest that SLAMF1 is another significant piece in the intricate defective immune-regulatory function of patients with SLE.
Asunto(s)
Antígenos CD/inmunología , Leucocitos Mononucleares/inmunología , Lupus Eritematoso Sistémico/inmunología , Receptores de Superficie Celular/inmunología , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Antígenos CD/biosíntesis , Autoinmunidad/inmunología , Procesos de Crecimiento Celular/inmunología , Femenino , Citometría de Flujo/métodos , Factores de Transcripción Forkhead/inmunología , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Persona de Mediana Edad , Receptores de Superficie Celular/biosíntesis , Miembro 1 de la Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Adulto JovenRESUMEN
Patients with systemic lupus erythematosus (SLE) show an enhanced risk to develop human papillomavirus (HPV) infection, and aggressive forms of this condition are seen in these patients. The aim of this study was to assess the possible relationship among HPV infection, immunosuppressive therapy and levels of leukocyte subsets in patients with SLE. The following individuals were included in the study: (1) SLE patients under immunosuppressive therapy and with lesions caused by HPV (n = 16); (2) SLE patients under immunosuppressive therapy and no evidence of HPV infection (n = 20); (3) untreated SLE patients with no evidence of HPV infection (n = 7), and; (4) healthy female subjects without evidence of HPV infection (n = 10). Peripheral blood was obtained and the percentages of different lymphocyte subsets were determined by flow cytometry, with the use of the following monoclonal antibodies: CD3, CD4, CD8, CD16, CD19, CD20, CD22, CD56, and CD335 (NKp46). We found that SLE patients under immunosuppressive therapy and with lesions caused by HPV showed significantly lower levels of B lymphocytes and NK cells compared to other groups. In contrast, SLE patients receiving immunosuppressive drugs and with no evidence of HPV infection showed similar levels of B and NK cells than healthy controls. Those patients receiving mycophenolate mofetil (MMF) had a diminished number of B cells, and a positive correlation was detected between the dose of MMF and the number of HPV skin lesions. Our data suggest that therapy of SLE patients with MMF is associated with diminished levels of B and NK cells and an enhanced risk for HPV infection.
Asunto(s)
Linfocitos B/patología , Células Asesinas Naturales/patología , Lupus Eritematoso Sistémico/inmunología , Papillomaviridae/inmunología , Infecciones por Papillomavirus/inmunología , Adulto , Circulación Sanguínea , Femenino , Humanos , Inmunidad Celular , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/etiología , Infecciones por Papillomavirus/prevención & control , Adulto JovenRESUMEN
Human papillomavirus (HPV) is able to inhibit the secretion of gamma interferon (IFN-γ) and the expression of some immune innate cell receptors. Immunoglobulin-like transcript 2 (ILT2) is a regulatory receptor that seems to participate in the pathogenesis of viral infections. We have studied the expression and function of ILT2 and the expression of other NK cell receptors in 23 healthy women before and after immunization with the quadrivalent HPV (type 6/11/16/18) vaccine (Gardasil). Receptor expression was analyzed by flow cytometry in freshly isolated peripheral blood mononuclear cells as well as after in vitro stimulation with the quadrivalent HPV (type 6/11/16/18) vaccine. In addition, the regulatory function of ILT2 on cell proliferation and IFN-γ production was analyzed. We found a significant increase in the expression of ILT2 by NK and CD3(+) CD56(+) lymphocytes and monocytes after quadrivalent HPV (type 6/11/16/18) vaccine immunization. In addition, the in vitro stimulation with the quadrivalent HPV (type 6/11/16/18) vaccine also increased the proportion of CD3(-) CD56(+) ILT2(+) NK cells. Although the inhibitory function of ILT2 on cell proliferation was enhanced after HPV immunization, the in vitro engagement of this receptor did not affect the synthesis of IFN-γ induced by HPV. Finally, a significant increase in the expression of NKG2D, NKp30, and NKp46 by NK and CD3(+) CD56(+) lymphocytes was detected after quadrivalent HPV (type 6/11/16/18) vaccine immunization. Our data indicate that HPV immunization is associated with significant changes in the expression and function of different innate immune receptors, including ILT2, which may participate in the protective effect of HPV vaccines.
Asunto(s)
Antígenos CD/biosíntesis , Inmunidad Innata , Vacunas contra Papillomavirus/administración & dosificación , Vacunas contra Papillomavirus/inmunología , Receptores Inmunológicos/biosíntesis , Adolescente , Adulto , Proliferación Celular , Femenino , Citometría de Flujo , Vacuna Tetravalente Recombinante contra el Virus del Papiloma Humano Tipos 6, 11 , 16, 18 , Humanos , Inmunofenotipificación , Interferón gamma/metabolismo , Células Asesinas Naturales/inmunología , Receptor Leucocitario Tipo Inmunoglobulina B1 , Linfocitos/inmunología , Monocitos/inmunología , Adulto JovenRESUMEN
The aim of this work was to study the expression and function of the inhibitory receptor ILT2/CD85j in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). We studied 23 SLE patients as well as 17 patients with rheumatoid arthritis, 10 with fibromyalgia, and 23 healthy individuals. We found a variable level of expression of ILT2 in the PBMC from both SLE patients and controls, with no significant differences among them. However, when the expression of this receptor was assessed in cell subsets, significantly lower levels were detected in CD19+ lymphocytes from SLE patients compared with healthy controls. Functional assays performed in unfractionated PBMC, showed a significant diminished inhibitory activity of ILT2 in CD4+ and CD8+ cell subsets from SLE patients compared to either rheumatoid arthritis or fibromyalgia patients, and healthy individuals. Our results show that the PBMC from some patients with SLE show a defective expression of ILT2, and that most of them exhibit a poor function of this inhibitory receptor.
Asunto(s)
Antígenos CD/fisiología , Leucocitos Mononucleares/inmunología , Lupus Eritematoso Sistémico/inmunología , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Receptores Inmunológicos/fisiología , Adulto , Antígenos CD/inmunología , Apoptosis , Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Estudios de Casos y Controles , Ciclo Celular , Células Cultivadas , Femenino , Fibromialgia/inmunología , Fibromialgia/metabolismo , Humanos , Receptor Leucocitario Tipo Inmunoglobulina B1 , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Activación de Linfocitos , Subgrupos Linfocitarios/citología , Masculino , Persona de Mediana Edad , Receptores Inmunológicos/inmunologíaRESUMEN
Tuberculosis remains one of the most important infectious diseases worldwide. Several studies have suggested that genetic factors may affect susceptibility to tuberculosis, but the specific genes involved have not yet been fully characterized. NRAMP1/SLC11 A1 and P2X(7) genes have been linked to increased risk for tuberculosis in some African and Asiatic populations. To explore the potential role of these genes in the susceptibility to pulmonary tuberculosis in a Mexican mestizo population, we evaluated the association of D543N and 3'-UTR polymorphisms in NRAMP1/SLC11 A1 and - 762 and A1513C polymorphisms in P2X(7) genes with the risk for tuberculosis. Polymerase chain reaction (PCR) amplification of genomic DNA followed by restriction fragment length polymorphism analysis, and allelic-specific PCR was employed. We found no significant differences in allelic frequency in NRAMP1/SLC11 A1 gene polymorphisms in 94 patients with tuberculosis compared to 100 healthy contacts. Similarly, no significant association of the P2X(7)-762 gene polymorphism with tuberculosis was detected. In contrast, the P2X(7) A1513C polymorphism was associated significantly with tuberculosis (P = 0.02, odds ratio = 5.28, 95% CI, 0.99-37.69), an association that had not been reported previously. However, when the function of P2X(7) was assessed by an L-selectin loss assay, we did not find significant differences in patients compared to healthy contacts or between PPD(+) and PPD(-) control individuals. This study further supports the complex role of P2X(7) gene in host regulation of Mycobacterium tuberculosis infection, and demonstrates that different associations of gene polymorphisms and tuberculosis are found in distinct racial populations.
Asunto(s)
Proteínas de Transporte de Catión/genética , Polimorfismo de Longitud del Fragmento de Restricción , Receptores Purinérgicos P2/genética , Tuberculosis Pulmonar/genética , Estudios de Casos y Controles , Proteínas de Transporte de Catión/sangre , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Selectina L/sangre , Leucocitos Mononucleares/metabolismo , Masculino , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/genética , Receptores Purinérgicos P2/sangre , Receptores Purinérgicos P2/fisiología , Receptores Purinérgicos P2X7 , Tuberculosis Pulmonar/sangreRESUMEN
P2X(7) is a channel receptor gated by adenosine triphosphate (ATP) that is involved in the killing of intracellular mycobacteria. To explore further the role of P2X(7) in immunity against Mycobacterium tuberculosis, we studied its expression and function in 19 patients with pulmonary tuberculosis (TB) and 19 healthy contacts. Flow cytometry analysis showed a similar and variable expression of P2X(7) in TB patients and healthy subjects. In contrast, P2X(7) mARN levels were significantly higher in TB patients. When the function of the P2X(7) receptor in peripheral blood mononuclear cells (PBMC) was assessed by the effect of exogenous ATP on apoptosis, the uptake of the fluorescent marker Lucifer yellow or extracellular signal regulated kinase (ERK) phosphorylation, no significant differences were detected in patients and controls. However, mRNA macroarray analysis showed that upon stimulation with ATP, the PBMC from TB patients showed a significant induction of a higher number of cytokine genes (27 of 96), and a lower number of apoptosis genes (20 of 96) compared to healthy controls (17 and 76 genes, respectively). These results suggest that although the PBMC from TB patients do not show apparent abnormalities in the expression of P2X(7), and the intracellular signals generated through it, the pattern of gene expression induced by ATP in these cells is different from that found in healthy contacts. This phenomenon suggests a defective function of P2X(7) in the immune cells from TB patients, a condition that may contribute to the inability of these patients to eliminate the mycobacteria.
Asunto(s)
Receptores Purinérgicos P2/sangre , Tuberculosis Pulmonar/inmunología , Adenosina Trifosfato/farmacología , Adolescente , Adulto , Anciano , Apoptosis/efectos de los fármacos , Apoptosis/genética , Western Blotting , Células Cultivadas , Femenino , Citometría de Flujo , Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/inmunología , Receptores Purinérgicos P2X7RESUMEN
OBJECTIVE: To assess the expression and function of the receptor for interleukin-10 (IL-10R) in immune cells from patients with systemic lupus erythematosus (SLE). METHODS: We assessed the expression and function of IL-10R in peripheral blood mononuclear cells (PBMCs) from 19 SLE patients and 15 healthy controls. The expression of IL-10R was assessed by flow cytometry, and the function of this receptor was determined by analysing both the activation of Jak-1, Tyk-2, Stat-1, and Stat-3 (Western blot) and the induction of gene expression (cDNA array test of 242 genes of cytokines, apoptosis and intracellular signalling) upon stimulation with IL-10. RESULTS: We found similar levels of IL-10R expression in SLE patients and controls. In addition, variable levels of Jak-1, Tyk-2, Stat-1, and Stat-3 activation were induced by IL-10 in PBMCs from SLE patients and controls, with no significant differences in protein phosphorylation or kinetics of activation. However, clear-cut differences in the gene expression induced through IL-10R were observed in SLE patients and controls, mainly in the genes involved in apoptosis and those encoding for cytokines and their receptors. CONCLUSIONS: Our data suggest that despite normal levels of IL-10R expression, and an apparent lack of abnormalities in the intracellular signals induced through this receptor, immune cells from SLE patients exhibit an aberrant pattern of gene expression induced through the IL-10R.
Asunto(s)
Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Receptores de Interleucina-10/metabolismo , Adolescente , Adulto , ADN/genética , Femenino , Regulación de la Expresión Génica/genética , Regulación Enzimológica de la Expresión Génica/genética , Humanos , Janus Quinasa 1/genética , Janus Quinasa 1/metabolismo , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/patología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/patología , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Receptores de Interleucina-10/genética , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , TYK2 Quinasa/genética , TYK2 Quinasa/metabolismoRESUMEN
We have explored the therapeutic potential of statins in patients with different inflammatory rheumatic diseases refractory to conventional therapy. We found that simvastatin (80mg o.d. for eight days) induced a rapid and significant reduction in proteinuria levels in three systemic lupus erythematosus (SLE) patients. A similar kind of therapy had a marked beneficial effect in a patient with Wegener's granulomatosis and a patient with erythema nodosum. On the other hand, five patients with rheumatoid arthritis (RA) who received atorvastatin for eight days (20mg/day) showed reduction in C-reactive protein levels and a clinical improvement that was classified as an ACR20 response. Prior to the administration of statins, all these patients had received aggressive conventional therapy with no satisfactory response. A significant reduction in spontaneous apoptosis of peripheral blood lymphocytes and expression of CD69 and HLA-DR was observed in SLE patients after simvastatin therapy. These results prompted us to perform a pilot short-time comparative (simvastatin versus chloroquine) open clinical trial in 15 patients with RA who were receiving methotrexate as a single disease modifying antirheumatic drug with no satisfactory response. Most patients (9/10) who received simvastatin (40mg/day) showed an ACR50 or better response after eight weeks, whereas such a response was not observed in any patient (0/5) treated with chloroquine. Our preliminary results indicate that statins may be an important therapeutic tool for the treatment of inflammatory rheumatic diseases.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedades Reumáticas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antirreumáticos/uso terapéutico , Atorvastatina , Biomarcadores/sangre , Sedimentación Sanguínea/efectos de los fármacos , Proteína C-Reactiva/efectos de los fármacos , Proteína C-Reactiva/metabolismo , Niño , Cloroquina/uso terapéutico , Relación Dosis-Respuesta a Droga , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/metabolismo , Antígenos HLA-DR/efectos de los fármacos , Antígenos HLA-DR/metabolismo , Ácidos Heptanoicos/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Leucocitos Mononucleares/efectos de los fármacos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/metabolismo , Persona de Mediana Edad , Proteinuria/inducido químicamente , Proteinuria/metabolismo , Pirroles/uso terapéutico , Enfermedades Reumáticas/metabolismo , Fiebre Reumática/tratamiento farmacológico , Fiebre Reumática/metabolismo , Simvastatina/uso terapéutico , Resultado del TratamientoRESUMEN
The aim of this work was to investigate the effect of cadmium, lead and arsenic on the apoptosis of human immune cells. Peripheral blood mononuclear cells (MNC) were incubated with increasing concentrations of these metals and then cellular apoptosis was determined by flow cytometry and by DNA electrophoresis. We found that arsenic induced a significant level of apoptosis at 15 microM after 48h of incubation. Cadmium had a similar effect, but at higher concentrations (65 microM). In addition, cadmium exerted a cytotoxic effect on MNC that seemed to be independent of the induction of apoptosis. In contrast, concentrations of lead as high as 500 microM were nontoxic and did not induce a significant degree of apoptosis. Additional experiments showed that arsenic at concentrations as low as 1.0 microM had a significant pro-apoptotic effect when cells were cultured in the presence of this pollutant for more than 72. Non-T cells were more susceptible than T lymphocytes to the effect of arsenic and cadmium. Interestingly, MNC from children chronically exposed to arsenic showed a high basal rate of apoptosis and a diminished in vitro sensibility to this metalloid. Our results indicate that both arsenic and cadmium are able to induce apoptosis of lymphoid cells, and suggest that this phenomenon may contribute to their immunotoxic effect in vivo.
Asunto(s)
Apoptosis/efectos de los fármacos , Arsénico/efectos adversos , Cadmio/efectos adversos , Contaminantes Ambientales/efectos adversos , Plomo/efectos adversos , Leucocitos Mononucleares/efectos de los fármacos , Adulto , Arsénico/orina , Arsenitos/farmacología , Arsenitos/toxicidad , Cloruro de Cadmio/farmacología , Cloruro de Cadmio/toxicidad , Células Cultivadas/efectos de los fármacos , Niño , Creatinina/orina , Relación Dosis-Respuesta a Droga , Exposición a Riesgos Ambientales , Humanos , Síndromes de Inmunodeficiencia/inducido químicamente , Leucocitos Mononucleares/citología , México , Minería , Compuestos Organometálicos/farmacología , Compuestos Organometálicos/toxicidad , Formación de Roseta , Compuestos de Sodio/farmacología , Compuestos de Sodio/toxicidad , Linfocitos T/citología , Linfocitos T/efectos de los fármacosRESUMEN
BACKGROUND: The involution of the central pigmented lesion in halo nevus (HN) seems to be mediated by an immune response against self antigens expressed by melanocytes. OBJECTIVE: We assessed the presence of activated lymphocytes in the peripheral blood lymphocytes from patients with HN. METHODS: Peripheral blood was obtained from patients with HN associated with benign pigmented lesions (5) or melanoma (2) as well as from patients with melanoma without HN (5) and healthy subjects (10). Activated lymphocytes were detected by flow cytometry analysis using monoclonal antibodies (mAb) against CD69, CD71, CD98, HLA-DR, and activated beta(1) integrins (HUTS-21 mAb). RESULTS: The peripheral blood lymphocytes from patients with HN, associated with either benign or malignant lesions, exhibited a significantly higher expression of all activation markers studied compared with patients with melanoma without HN or compared with healthy subjects. Therefore the peripheral blood of HN patients contained a significant fraction of lymphocytes with an activated (CD69(+), HLA-DR(+), CD98(bright)), cell proliferating (CD71( bright)), and high adhesive (HUTS-21(bright)) phenotype. These activated cells disappeared from peripheral blood after the surgical resection of the skin lesion. CONCLUSION: Our findings further support the involvement of immune activation in HN phenomenon.
Asunto(s)
Antígenos CD/análisis , Activación de Linfocitos , Nevo Pigmentado/sangre , Neoplasias Cutáneas/sangre , Adolescente , Adulto , Niño , Femenino , Citometría de Flujo , Antígenos HLA-DR/análisis , Humanos , Masculino , Melanoma/sangre , Melanoma/inmunología , Persona de Mediana Edad , Nevo Pigmentado/inmunología , Neoplasias Cutáneas/inmunologíaRESUMEN
Actinic prurigo is an inflammatory disease of the skin that appears to be mediated by an abnormal immune response. Cell adhesion molecules play a key role in the induction of the immune response as well as in the pathogenesis of inflammation. We investigated the expression of cell adhesion and activation molecules, as well as the density of Langerhans cells in skin from patients with actinic prurigo. Skin biopsies from ultraviolet light-induced lesions, and non-irradiated areas from 10 actinic prurigo patients were studied; in addition, several spontaneous skin lesions were studied. Skin biopsies from normal individuals were used as controls. The expression of ICAM-1, ICAM-3, LFA-3, CD2, LFA-1, VLA-4, CD1a, VCAM-1, CD69, and activated b1 integrins were assessed by immunostaining. An increased expression of LFA-1, LFA-2, ICAM-3, VLA-4, and activated b1 integrins was observed in the cell infiltrate of actinic prurigo lesions and an up-regulated expression of ICAM-1 was detected in keratinocytes from these specimens. Interestingly, the number of Langerhans cells (CD1a + ) in actinic prurigo skin was not significantly affected by ultraviolet irradiation, a phenomenon that was not observed in normal controls. The increased expression of adhesion molecules in the cell infiltrate of actinic prurigo, indicates that these cells are activated and suggests that they are involved in the skin damage seen in these patients. The resistance of Langerhans cells from patients with actinic prurigo to ultraviolet light may have an important role in the pathogenesis of this condition. The involvement of keratinocytes in the pathogenesis of actinic prurigo is suggested by the expression of ICAM-1 on these cells.
Asunto(s)
Moléculas de Adhesión Celular/análisis , Células de Langerhans/patología , Células de Langerhans/efectos de la radiación , Prurigo/patología , Rayos Ultravioleta , Anticuerpos Monoclonales/análisis , Biopsia con Aguja , Células Cultivadas , Humanos , Molécula 1 de Adhesión Intercelular/análisis , Queratinocitos/química , Valores de Referencia , Molécula 1 de Adhesión Celular Vascular/análisisRESUMEN
OBJECTIVES: To assess the expression of several cell adhesion and lymphocyte activation molecules in erythema dyschromicum perstans lesions, and to evaluate the effect of clofazimine therapy on the expression of these molecules. DESIGN AND METHODS: A prospective study. Skin biopsy samples were obtained from patients before and after 3 months of clofazimine therapy, and the expression of cell adhesion and activation molecules was assessed by an immunohistochemical technique. SETTING: This study was performed in a clinical referral center and an immunology research laboratory. PATIENTS: We studied 6 patients with erythema dyschromicum perstans. A diagnosis was made on the basis of clinical and histological criteria. Two patients discontinued participation in the study: one because of adverse effects and the other for unknown reasons. INTERVENTIONS: Patients were treated with clofazimine, 100 mg/d, for 3 months. MAIN OUTCOME MEASURES: Expression of cell adhesion and lymphocyte activation molecules in skin biopsy specimens before and after clofazimine therapy. RESULTS: Before clofazimine therapy, we detected a noticeable expression of intercellular adhesion molecule 1 and major histocompatibility complex class II molecules (HLA-DR) in the keratinocyte basal cell layer. In addition, CD36, a thrombospondin receptor that is not expressed by normal skin, was detected in the strata spinosum and granulosum. The dermal cell infiltrate expressed the activation molecule AIM/CD69 and the cytotoxic cell marker CD94. After clofazimine therapy, the expression of intercellular adhesion molecule 1 and HLA-DR disappeared, as well as the mononuclear cell infiltrate. CONCLUSIONS: Our results suggest that some cell adhesion and activation molecules are involved in the pathogenesis of erythema dyschromicum perstans. Clofazimine appears to have an important effect on the inflammatory phenomenon of erythema dyschromicum perstans.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Antígenos CD/biosíntesis , Moléculas de Adhesión Celular/biosíntesis , Clofazimina/uso terapéutico , Eritema/etiología , Trastornos de la Pigmentación/etiología , Eritema/tratamiento farmacológico , Eritema/inmunología , Humanos , Activación de Linfocitos , Trastornos de la Pigmentación/tratamiento farmacológico , Trastornos de la Pigmentación/inmunologíaRESUMEN
We studied the plasma levels of tumor necrosis factor-alpha (TNF-alpha) interleukin-6 (IL-6) as well as the in vitro production of these cytokines by peripheral blood mononuclear cells, in 10 patients with amebic liver abscess (ALA) and seven healthy controls. TNF-alpha was measured using a bioassay with L929 fibroblasts; IL-6 was quantitated by the B9 cell line assay. In both assays, the number of viable cells was estimated by the conversion of MTT to formazan. TNF-alpha plasma levels were nondetectable (< 20 pg/mL) in ALA patients, as well as in the majority of healthy controls. The in vitro production of TNF induced by lipopolysaccharide was significantly decreased in ALA patients. Most ALA patients (8/10) had increased plasma levels of IL-6. Furthermore, the spontaneous production of IL-6 in vitro was significantly increased in ALA patients compared to controls. In the acute stage of the ALA, a negative relationship was found between the raised plasma levels of IL-6 and the in vitro diminished production of TNF-alpha. After recovery, ALA patients showed both normal plasma levels and in vitro production of TNF and IL-6. Our data corroborate previous reports regarding plasma levels of TNF in ALA, and suggest that E. histolytica induces the in vivo production of IL-6 through a TNF-independent pathway. The raised levels of IL-6 might in turn down-regulate the production of TNF in ALA patients.
Asunto(s)
Interleucina-6/biosíntesis , Absceso Hepático Amebiano/sangre , Factor de Necrosis Tumoral alfa/biosíntesis , Enfermedad Aguda , Animales , Línea Celular , Convalecencia , Humanos , Interleucina-6/sangre , Células L , Leucocitos Mononucleares/metabolismo , Ratones , Factor de Necrosis Tumoral alfa/análisisRESUMEN
BACKGROUND: The pathogenesis of autoeczematization (AE) is not well understood; however, previous studies suggest that AE is an autoimmune condition. OBJECTIVE: Our purpose was to assess whether AE is associated with an abnormal immune recognition of autologous skin antigens. METHODS: Eight patients with AE, six healthy control subjects, and three patients with localized contact dermatitis (LCD) were studied. Activation markers were detected on peripheral blood T lymphocytes. Autologous mixed epidermal cell-lymphocyte reaction (AMECLR) was performed for each subject and cell proliferation was assessed by tritiated thymidine incorporation. RESULTS: Many activated T cells were detected in patients with AE (5.2% +/- 4.5% vs 0.2% +/- 0.4% in control subjects, p < 0.05). AMECLR showed a significantly higher cell proliferation in AE compared with both healthy subjects and patients with LCD (6372 +/- 3217 cpm vs 2638 +/- 1788 cpm, and 2471 +/- 1389 cpm, respectively; p < 0.05). Peripheral blood mononuclear cells cultured in the presence of an autologous skin homogenate also showed a significantly increased cell proliferation in patients with AE than in control subjects. CONCLUSION: Our results suggest that an abnormal immune response against autologous skin antigens occurs in AE that could be related to the pathogenesis of this disease.
Asunto(s)
Autoantígenos/inmunología , Enfermedades Autoinmunes/inmunología , Dermatitis/inmunología , Eccema/inmunología , Piel/inmunología , Enfermedad Crónica , Humanos , Leucocitos Mononucleares/inmunología , Prueba de Cultivo Mixto de Linfocitos , Piel/citología , Subgrupos de Linfocitos T/inmunologíaRESUMEN
There are evidences regarding the role of NK cytotoxic activity in the resistance against experimental C. neoformans infection. To assess the status of NK cell activity in human C. neoformans infection, we studied the peripheral blood of twelve patients with cryptococcal meningitis, six patients with CNS disease different to cryptococcal meningitis, and twelve healthy subjects. The number of CD16+cells and the NK cytotoxic activity of peripheral blood mononuclear cells was studied. The in vitro effect of exogenous IL-2 and interferon gamma on such cytotoxic activity was also studied. The number of CD16+ cells was not significantly different in patients compared to controls. However, cryptococcal patients exhibited a significant lower NK activity compared to both control groups (p less than 0.05 in both cases). The low NK activity of cryptococcal patients was fully reconstituted in vitro with the addition of rIL-2 but not with rIFN gamma. In vitro experiments suggest that the low NK activity of cryptococcal meningitis patients is not due to amphotericin B therapy or blockade of NK cells by C. neoformans-derived molecules. The results of this study suggests that patients with cryptococcal meningitis have a defective NK cytotoxic function and may aid to understand the pathogenesis of this disease.
Asunto(s)
Citotoxicidad Inmunológica , Células Asesinas Naturales/inmunología , Meningitis Criptocócica/inmunología , Adulto , Femenino , Humanos , MasculinoRESUMEN
To get further insight into the pathogenesis of polymorphous light eruption, we studied nine patients with polymorphous light eruption and six healthy persons. Two skin biopsy specimens were obtained from each person, one from previously ultraviolet light-irradiated skin and another one from unirradiated skin. An epidermal cell suspension, skin homogenate, or both were prepared from each specimen. Autologous cultures were made with peripheral blood mononuclear cells combined with irradiated or unirradiated skin homogenate and peripheral blood mononuclear cells combined with irradiated or unirradiated epidermal cell suspension. Cell proliferation was assessed by 3H-thymidine incorporation assay. The response of peripheral blood mononuclear cells to unirradiated epidermal cells or unirradiated skin homogenate was similar in both patients and controls. However, peripheral blood mononuclear cells from patients with polymorphous light eruption showed a significantly increased proliferative response to both irradiated epidermal cells and irradiated skin homogenate. Our results indicate that ultraviolet light increases the stimulatory capability of polymorphous light eruption epidermal cells in a unidirectional mixed culture with autologous peripheral blood mononuclear cells. This suggests that an immune sensitization against autologous ultraviolet light-modified skin antigens occurs in polymorphous light eruption.