RESUMEN
We studied the effects of hormone replacement therapy (HRT) with estrogen on postmenopausal changes in the production of bone-resorbing cytokines interleukin 1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha). Both cytokines were measured in the supernatants of lipopolysaccharide (LPS)-stimulated whole-blood cells from 72 untreated and 44 HRT-treated women by ELISA. The levels of IL-1beta were significantly higher in women in their 40s and 50s and in postmenopausal women than in women in their teens, 20s and 30s, while the levels of TNFalpha did not show any changes related to age. Both levels in HRT-treated women were significantly lower than those in untreated women at almost every postmenopausal stage. In a prospective study, HRT induced significant declines in both levels. These results show that estrogen decreases the accelerated production of IL-1beta and reduces the production of TNFalpha in postmenopausal women at each postmenopausal stage, even in late-postmenopausal women.
Asunto(s)
Células Sanguíneas/metabolismo , Resorción Ósea/metabolismo , Citocinas/metabolismo , Terapia de Reemplazo de Estrógeno , Adulto , Envejecimiento/metabolismo , Estudios Transversales , Femenino , Humanos , Lipopolisacáridos/farmacología , Persona de Mediana Edad , Estudios Prospectivos , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Twenty-five patients with pituitary lesions were operated on by image-guided transsphenoidal surgery (TSS) using the Mehrkoordinaten Manipulator (MKM) navigation system. The cases included 21 cases of pituitary adenomas, 2 cases of craniopharyngioma and 2 cases of Rathke's cleft cyst. All operations were performed through the sublabial approach under an operative microscope. In some cases, an endoscope was used for the observation of the residual tumor and surrounding structures. The tumors and surrounding important structures such as the internal carotid arteries, the basilar artery, and the optic nerves were precisely localized, and mechanical error was less than 2 mm in almost all cases. In 3 early cases of pituitary adenoma, the patient's head was moved slightly during the insertion of the nasal speculum; in these cases, the resulting error was more than 2 mm. In evaluating the procedures, we determined that the most useful benefit of the MKM system compared with other systems is that the navigation information is not only displayed on the monitor, but also presented in the operative field under the microscope. Therefore, the surgeon can obtain the navigation information without removing his eyes from the operative field under the microscope. The most important drawback to the system is its bulky size.
Asunto(s)
Adenoma/cirugía , Quistes del Sistema Nervioso Central/cirugía , Craneofaringioma/cirugía , Neuronavegación/instrumentación , Neoplasias Hipofisarias/cirugía , Seno Esfenoidal/cirugía , Cirugía Asistida por Computador/instrumentación , Adenoma/patología , Adolescente , Adulto , Anciano , Quistes del Sistema Nervioso Central/patología , Niño , Craneofaringioma/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Evaluación de Resultado en la Atención de Salud , Neoplasias Hipofisarias/patología , Seno Esfenoidal/patologíaRESUMEN
We investigated whether the measurement of serum interleukin 18 (IL-18) and intracellular cytokine analysis of peripheral blood CD4-positive T cells (ICA-CD4+ Tc) of chronic hepatitis C (CH-C) patients before and two weeks after interferon (IFN) administration are useful for predicting sustained response to IFN. Twenty-nine CH-C patients received IFN every day for two weeks and three times a week for 22 weeks. Patients were divided into two groups: responders, in whom serum HCV-RNA was undetectable at the end of the follow-up (week 48), and nonresponders, in whom any other patterns were seen. Before and two weeks after IFN administration, serum IL-18 and ICA-CD4+ Tc as described by Jung et al were measured. Serum IL-18 and the relative prevalence of IFN-gamma+ and IL-4+, IFN-gamma+ and IL-4 (Th-1), and IFN-gamma- and IL-4+ cells in the responders were significantly increased, but only the relative prevalence of Th-1 cells in the nonresponders was increased two weeks after IFN therapy. In conclusion, ICA-CD4+ Tc and the measurement of serum IL-18 might be useful for predicting IFN therapy by comparing the results between before and two weeks after IFN.
Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Citocinas/sangre , Hepatitis C Crónica/sangre , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Membranas Intracelulares/metabolismo , Femenino , Predicción , Hepatitis C Crónica/patología , Humanos , Interleucina-18/sangre , Hígado/patología , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/patologíaRESUMEN
To clarify the clinical significance of autoantibodies to interleukin-1 alpha (IL-1 alpha autoantibodies) in rapidly progressive idiopathic pulmonary fibrosis (IPF), we measured the level of IL-1 alpha autoantibodies in serum of 11 patients on the first hospital day, when patients were admitted due to severe symptoms, and on the 21st hospital day. IL-1 alpha autoantibodies in serum were measured using radioimmunoassay, and the limitation of this assay for IL-1 alpha autoantibodies was 5 ng/ml. These antibodies were detected in 5 of 11 patients on the first hospital day. On the 21st hospital day, these antibodies were detected in all patients, and its level was increased compared with that on the first hospital day. IL-1 alpha autoantibodies that appeared in patients corresponded to that of IgG. The half life of exogenous autoantibodies was investigated following administration of autoantibody rich plasma obtained from healthy blood donors to 6 control patients (CP) and 6 progressive IPF patients. These autoantibody levels in their serum were less than 5 ng/ml before administration. Serum was obtained at the indicated time after administration of IL-1 alpha autoantibodies and the level of these autoantibodies in serum was measured, then the half life was calculated. Half life of exogenous IL-1 alpha autoantibodies in progressive IPF patients was significantly shorter than that in CP (71.3 +/- 31.8 hr vs 352.0 +/- 98.3 hr, p < 0.01). These findings suggested that IL-1 alpha autoantibodies were generated in response to the inflammatory process of rapidly progressive IPF and may act as a regulatory factor for IL-1 alpha.
Asunto(s)
Autoanticuerpos/inmunología , Autoantígenos/inmunología , Interleucina-1/inmunología , Fibrosis Pulmonar/inmunología , Anciano , Antiinflamatorios/uso terapéutico , Autoanticuerpos/sangre , Progresión de la Enfermedad , Disnea/etiología , Femenino , Semivida , Humanos , Inmunosupresores/uso terapéutico , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Prednisolona/uso terapéutico , Fibrosis Pulmonar/sangre , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/tratamiento farmacológico , Fumar , Resultado del TratamientoRESUMEN
CC chemokine receptor (CCR)4 is selectively expressed on Th2-type T cells and has been shown to be responsible for Th2-dominant immune responses. In this study, we analyzed the expression of CCR4 in active systemic lupus erythematosus (SLE) patients by FACS analysis using anti-human CCR4 monoclonal antibody and determined the clinical relevance in this disease. Higher expression of CCR4 was found on peripheral blood CD4+ T lymphocytes of active SLE patients than was found with healthy controls and inactive SLE patients. The CCR4 expression significantly correlated with the SLE disease activity index (SLEDAI) scores. The expression was dramatically decreased after the corticosteroid therapy in parallel with a serum level of double-stranded DNA antibody and SLEDAI scores. Moreover, we found that serum levels of IL-10 were increased in active SLE patients and significantly correlated with the CCR4 expression. This study suggests that Th2 immune response is predominant in the active state of SLE, and CCR4 may have relevance in regard to the disease course in SLE patients.
Asunto(s)
Enfermedades Autoinmunes/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Receptores de Quimiocina/biosíntesis , Células Th2/metabolismo , Adolescente , Adulto , Anticuerpos Antinucleares/sangre , Anticuerpos Monoclonales/inmunología , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Femenino , Citometría de Flujo , Regulación de la Expresión Génica , Humanos , Inmunosupresores/uso terapéutico , Interleucina-10/sangre , Interleucina-4/análisis , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Receptores CCR4 , Receptores de Quimiocina/genética , Receptores de Quimiocina/inmunología , Índice de Severidad de la Enfermedad , Células Th2/inmunologíaRESUMEN
The aim of this study was to determine, at least in part, T-cell function in postmenopausal women and the effects of hormone replacement therapy (HRT). Levels of T-helper 1 (Th1) cytokines (IL-2 and IFN-gamma) and T-helper 2 (Th2) cytokines (IL-4 and IL-10) produced by phytohemagglutinin-stimulated whole blood cells from 72 untreated and 44 HRT-treated women were measured by ELISA. Thirteen of the 44 HRT-treated women were examined before and during HRT. The production of IL-2 increased gradually with advance of the postmenopausal period. The levels of IL-2 in women in the early (< or =10 years) and mid (>10 and <30 years) postmenopausal stages were significantly higher than those in women in their second, third and fourth decades. The level in women in the late (> or =30 years) postmenopausal stage, however, was significantly lower than those in women in the early and mid postmenopausal stages. The level of IFN-gamma was highest in women in the mid postmenopausal stage. On the other hand, the levels of Th2 cytokines did not change with age or after menopause until the mid postmenopausal period but were significantly lower in women in the late postmenopausal stage. IFN-gamma levels in women on HRT were significantly lower than those in untreated postmenopausal women at all postmenopausal stages. HRT induced a significant decrease in the production of IL-2 and IL-4. In conclusion, production of Th1 cytokines is augmented in women after menopause. HRT prevents this increase, thereby improving the aberration of Th1/Th2 balance that is implicated in an inadequate immune response and pathological conditions.
Asunto(s)
Citocinas/metabolismo , Terapia de Reemplazo de Estrógeno , Posmenopausia/metabolismo , Linfocitos T Colaboradores-Inductores/metabolismo , Adolescente , Adulto , Factores de Edad , Ensayo de Inmunoadsorción Enzimática , Estrógenos Conjugados (USP)/metabolismo , Femenino , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Acetato de Medroxiprogesterona/metabolismo , Persona de Mediana Edad , Fitohemaglutininas/metabolismoRESUMEN
Active immunization with the peptide segments rSMP-230 and YAL-198, corresponding to the hydrophilic extracellular domain of two human sperm antigens (rSMP-B and YWK-II, respectively), reduced fertility in female rats by different mechanisms. The anti-rSMP-230 antibody interferes with human and murine fertilization, and the anti-YAL-198 antibody blocks the development of mouse embryos. The authors examined in vitro at which stage the antibodies to rSMP-230 and YAL-198 were cytotoxic to murine embryos up to morula/blastocyst stage. Anti-rSMP-230 antibody was not cytotoxic to any stages. On the other hand, the anti-YAL-198 antibody arrested the growth of embryos at the 2-cell stage but not at more advanced developmental stages. When the anti-YAL-198 antibody was used, spotty staining was observed only on the surfaces of embryos that had arrested at the 2-cell stage. Unstained embryos, however, continued to develop normally. In contrast, the anti-rSMP-230 antibody stained murine sperm but failed to stain murine ova and embryos. The present results suggest that the human sperm components rSMP-B and YWK-II play important roles in sperm-egg interaction and early development of the embryo, respectively.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígenos/inmunología , Citotoxicidad Inmunológica , Espermatozoides/inmunología , Animales , Desarrollo Embrionario y Fetal/inmunología , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Masculino , Ratas , Interacciones Espermatozoide-Óvulo/inmunologíaRESUMEN
In view of a cytoprotective effect of elastase inhibitor on chemokine-mediated tissue injury, we examined the neuroprotective effect of ONO-5046, a specific inhibitor of neutrophil elastase, in rats with spinal cord injury. Standardized spinal cord compression markedly increased cytokine-induced neutrophil chemo-attractant (CINC)-1 mRNA and protein. Their increases correlated with neurologic severity of injured rats. Immunohistochemically, CINC-1 protein was detected sequentially in vascular endothelial cells at 4 h, in perivascular neutrophils at 8 h, and in neutrophils infiltrating into cord substance at 12 h. Pretreatment with ONO-5046 (50 mg/kg) markedly ameliorated motor disturbance in injured rats, and reduced CINC-1 protein and mRNA expression. ONO-5046 also significantly reduced the increase of neutrophil accumulation or infiltration estimated by myeloperoxidase activity, and the extent of vascular permeability by Evans blue extravasation in the injured cord segment in comparison to control animals receiving vehicle. These results suggest that CINC-1 contributed to inflammation in rat spinal cord injury and ONO-5046 attenuated neurologic damage partly by blocking CINC-1 production of the chemoattractant, preventing neutrophil activation and vascular endothelial cell injury.
Asunto(s)
Quimiocinas CXC , Glicina/farmacología , Péptidos y Proteínas de Señalización Intercelular , Elastasa de Leucocito/antagonistas & inhibidores , Inhibidores de Serina Proteinasa/farmacología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Sulfonamidas/farmacología , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/fisiología , Quimiocina CXCL1 , Factores Quimiotácticos/análisis , Factores Quimiotácticos/genética , Factores Quimiotácticos/inmunología , Expresión Génica/efectos de los fármacos , Expresión Génica/inmunología , Glicina/análogos & derivados , Sustancias de Crecimiento/análisis , Sustancias de Crecimiento/genética , Sustancias de Crecimiento/inmunología , Inmunohistoquímica , Interleucina-8/inmunología , Elastasa de Leucocito/metabolismo , Actividad Motora/efectos de los fármacos , Peroxidasa/metabolismo , ARN Mensajero/análisis , Ratas , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Médula Espinal/enzimología , Médula Espinal/inmunología , Traumatismos de la Médula Espinal/inmunologíaRESUMEN
Gastric carcinoma cells express potent angiogenic factors including vascular endothelial growth factor (VEGF). We previously reported that interleukin-8 (IL-8) acts as an angiogenic factor for human gastric carcinomas. More recently, we found that IL-8 upregulates matrix metalloproteinase-9 (MMP-9) expression and increases invasive activity of gastric carcinoma cells. The purpose of this study was to determine whether the expression of IL-8 and VEGF correlates with clinicopathological parameters in human gastric carcinomas. IL-8 and VEGF expression levels were measured by an enzyme-linked immunosorbent assay (ELISA) in 56 gastric carcinomas and the surrounding normal mucosa. Macroscopic and histopathological tumour findings, presence of metastasis and prognosis were obtained from the patient records and endoscopic, surgical and pathological reports. IL-8 protein levels were higher in most neoplasms than in the corresponding normal mucosal tissue. In contrast, VEGF expression in the tumours was similar to that in normal mucosa. The IL-8 level in the neoplasms correlated significantly with the depth of invasion, venous invasion and lymphatic invasion. VEGF expression in the tumours correlated well with the depth of invasion and lymph node metastasis. No correlation between IL-8 and VEGF expression in the tumours was observed. The survival rates of patients with tumours displaying high IL-8 and VEGF expression levels were significantly lower (P<0.05) than those of patients with tumours displaying low IL-8 and VEGF expression. The results suggest that IL-8 and VEGF may be independent and important prognostic factors in human gastric carcinomas.
Asunto(s)
Factores de Crecimiento Endotelial/metabolismo , Interleucina-8/metabolismo , Linfocinas/metabolismo , Neoplasias Gástricas/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Mucosa Gástrica/irrigación sanguínea , Mucosa Gástrica/metabolismo , Humanos , Metástasis Linfática/diagnóstico , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica/diagnóstico , Neovascularización Patológica/diagnóstico , Pronóstico , Neoplasias Gástricas/metabolismo , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
Although elastase could affect sperm motility in vitro, secretory leukocytes protease inhibitor (SLPI) prevents sperm from being attacked by elastase. The authors investigated the correlations of elastase level with sperm motility and SLPI level in vivo. Semen samples (n = 116) were collected and centrifuged after semen analysis. Elastase and SLPI levels were determined by an enzyme immunosorbent assay. Samples were classified by elastase levels into low (<250 ng/mL), moderate (250-1,000 ng/mL), and high elastase groups (> or =1,000 ng/mL). Elastase levels (range, 2.8-23,974.4 ng/mL) were not associated with sperm motility. The median SLPI level in the high elastase group was 15,900 ng/mL (range, 2.860-46,900 ng/mL). However, there was no significant correlation between elastase and SLPI levels in seminal plasma. Since SLPI forms a 1:1 complex with elastase, these results suggest that seminal plasma has a sufficient amount of SLPI to protect spermatozoa from elastase.
Asunto(s)
Elastasa de Leucocito/análisis , Semen/enzimología , Motilidad Espermática , Inhibidores Enzimáticos/análisis , Humanos , Técnicas para Inmunoenzimas , Elastasa de Leucocito/antagonistas & inhibidores , Masculino , Proteínas Inhibidoras de Proteinasas Secretoras , Proteínas/análisis , Inhibidor Secretorio de Peptidasas LeucocitariasRESUMEN
OBJECTIVE: An appropriate defense against infective agents or malignant cells is attributed to the exquisitely balanced T helper 1 type (cellular) and T helper 2 type (humoral) immune reactions. We investigated the effect of hormone replacement therapy (HRT) on postmenopausal changes in the production of interferon (IFN)-gamma and interleukin (IL)-10, a type 1 and a type 2 cytokine, respectively. DESIGN: Both cytokines were measured by ELISA in the supernatant of lipopolysaccharide-stimulated whole blood cells from 72 untreated and 44 HRT-treated women. Thirteen women were examined before and during HRT. RESULTS: The production of IFN-gamma in women in their 40s and in postmenopausal women was significantly higher compared with that of younger women. However, IFN-gamma fell to the lowest level in the late postmenopausal stage, whereas the production of IL-10 increased gradually with age and in parallel with the postmenopausal period. Thus, in women in the mid-and late postmenopausal period, excessive production of type 2 cytokine (IL-10) compared with type 1 cytokine (IFN-gamma) occurred. The IFN-gamma levels of women on HRT were significantly lower than those of untreated women in the early and mid-postmenopausal stages, and IL-10 levels of women on HRT were significantly lower than those of untreated women in the mid-and late postmenopausal stages. HRT induced a significant decrease in the production of IL-10 and tended to lower the level of IFN-gamma. CONCLUSIONS: Production of IL-10 is augmented in postmenopausal women. HRT probably prevents postmenopausal women from an aberration of the immune system by improving the balance of type 1 and type 2 immune reactions.
Asunto(s)
Citocinas/efectos de los fármacos , Terapia de Reemplazo de Estrógeno , Interferón gamma/efectos de los fármacos , Interferón gamma/inmunología , Interleucina-10/inmunología , Posmenopausia/efectos de los fármacos , Posmenopausia/inmunología , Adulto , Anciano , Citocinas/sangre , Citocinas/clasificación , Citocinas/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Persona de Mediana Edad , Premenopausia/inmunología , Estudios ProspectivosRESUMEN
To determine whether sperm membrane components, rSMP-B and YWK-II, are suitable candidates as immunocontraceptives in humans, antifertility activities of the antibodies to the peptide fragments, rSMP-229 and rSMP-230 of rSMP-B and YAL-198 of YWK-II, were examined. In a previous report, anti-rSMP-230 antibody was shown to immobilise human sperm and to block human fertilisation, and the antigen (rSMP-230) to interact with antisperm antibodies found in sera of infertile women. Antibody to the second synthetic peptide, rSMP-229, corresponding to a different segment of rSMP-B, mimicked the biological activities of the anti-rSMP-230 antibody. Anti-YAL-198 antibody significantly, although weakly, inhibited human fertilisation. In the murine model, the anti-rSMP-B antibodies blocked in vitro fertilisation of mouse eggs but had no influence on embryo growth. Anti-YAL-198 antibody, however, arrested the growth of zygotes. In conclusion, rSMP-B, a human sperm protein, is a promising candidate in the development of an immunocontraceptive for human application. A second sperm protein, YWK-II, is effective as an antifertility immunogen in experimental animals.
Asunto(s)
Precursor de Proteína beta-Amiloide , Anticuerpos/inmunología , Antígenos de Superficie , Antígenos/inmunología , Anticoncepción Inmunológica/métodos , Infertilidad/inmunología , Proteínas de la Membrana/inmunología , Proteínas del Tejido Nervioso , Espermatozoides/inmunología , Animales , Anticuerpos/farmacología , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Femenino , Fertilización In Vitro/efectos de los fármacos , Humanos , Sueros Inmunes/inmunología , Sueros Inmunes/farmacología , Infertilidad/inducido químicamente , Masculino , Ratones , Modelos Animales , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/inmunología , Interacciones Espermatozoide-Óvulo/efectos de los fármacosRESUMEN
Nine new sesquiterpene pyridine alkaloids [wilfornines A (1), B (2), C (3), D (4), E (5), F (8), and G (9); wilfordinines I (6) and J (7)] and six known compounds (10-15) were isolated from a clinically used extract (T(II)) of Tripterygium wilfordii. The structures of 1-9 were elucidated by spectroscopic and chemical methods. The inhibitory effects on cytokine production of 1-3 and several related compounds were evaluated. Compounds 10 and 14 showed significant inhibitory effects on cytokine production.
Asunto(s)
Alcaloides/farmacología , Inmunosupresores/farmacología , Plantas Medicinales/química , Sesquiterpenos/farmacología , Alcaloides/aislamiento & purificación , Antiinflamatorios/farmacología , China , Citocinas/biosíntesis , Humanos , Inmunosupresores/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Prednisolona/farmacología , Sesquiterpenos/aislamiento & purificación , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría InfrarrojaRESUMEN
Aerial parts of Daphne oleoides Schreber ssp. oleoides (Thymelaeaceae) are used to treat rheumatoid arthritis and lumbago in Turkish folk medicine. In order to evaluate folkloric utilization, in vitro inhibitory effects of the ethyl acetate extract and fractions obtained from this extract on interleukin 1 (IL-1alpha, IL-1beta) and tumour necrosis factor (TNF-alpha) biosynthesis were studied. Through chemical isolation techniques and activity-guided fractionation process, seventeen compounds were isolated and their structures were elucidated (numbered 1-17). Diterpenoids genkwadaphnin (3) and 1,2-dehydrodaphnetoxin (6) and a coumarin derivative daphnetin (9) showed potent inhibitory activity and were found to be the main active ingredients. Furthermore, gnidilatin (4), gnidilatin-20 palmitate (5), genkwadaphnin-20-palmitate (7) and gnidicin-20-palmitate (8), having diterpenoid structure, and eudesmine (12), wikstromol (13) and matairesinol (14), having lignan structure, were determined to possess moderate inhibitory activity and may have a contributory role in the effect of the remedy.
Asunto(s)
Citocinas/metabolismo , Extractos Vegetales/farmacología , Acetatos/farmacología , Antineoplásicos Fitogénicos/farmacología , Diterpenos/farmacología , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Depuradores de Radicales Libres/farmacología , Furanos/farmacología , Humanos , Interleucina-1/biosíntesis , Interleucina-1/sangre , Lignanos/farmacología , Modelos Químicos , Plantas Medicinales/química , Factor de Necrosis Tumoral alfa/biosíntesis , Umbeliferonas/farmacologíaRESUMEN
BACKGROUND/AIMS: The aim of this study was to evaluate the inflammatory or antiinflammatory cytokine response to ischemia-reperfusion during hepatectomy and to find a useful marker of injury or surgical stress during hepatic ischemia-reperfusion. METHODOLOGY: In 9 patients with liver disease who underwent hepatectomy using the Pringle maneuver, serum cytokines, including alanine transaminase, aspartate transaminase, and hyaluronic acid, were measured just prior to vascular occlusion; 5, 10 and 15 min after initial clamping; and 3 min after initial declamping. RESULTS: The mean concentrations of aspartate transaminase and alanine transaminase did not significantly differ before and after ischemia-reperfusion during hepatectomy. However, mean concentrations of hyaluronic acid after ischemia-reperfusion were significantly (P < 0.03) higher than before clamping. Although there were no significant differences in the mean concentrations of IL-1 beta, IL-6, IL-8, IL-10 and TNF-alpha among, before and after ischemia-reperfusion, the mean concentrations of granulocyte colony-stimulating factor after ischemia-reperfusion and macrophage colony-stimulating factor after reperfusion were significantly (P < 0.05) higher than before clamping. CONCLUSIONS: Although hepatic parenchymal cell function was maintained after ischemia-reperfusion during hepatectomy, sinusoidal endothelial cell dysfunction was found. Release of granulocyte colony-stimulating factor and macrophage colony-stimulating factor after ischemia-reperfusion were also found. These cytokines and hyaluronic acid may be useful indicators in the early phase of human ischemia-reperfusion injury during hepatectomy.
Asunto(s)
Citocinas/sangre , Hepatectomía/efectos adversos , Hígado/irrigación sanguínea , Daño por Reperfusión/diagnóstico , Estrés Fisiológico/diagnóstico , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Femenino , Factor Estimulante de Colonias de Granulocitos/sangre , Técnicas Hemostáticas/efectos adversos , Humanos , Ácido Hialurónico/sangre , Interleucinas/sangre , Factor Estimulante de Colonias de Macrófagos/sangre , Masculino , Persona de Mediana Edad , Daño por Reperfusión/etiología , Estrés Fisiológico/etiología , Factor de Necrosis Tumoral alfa/análisisRESUMEN
BACKGROUND: The mechanisms of the reported high increase in interleukin-6 (IL-6) levels after esophagectomy are unclear. We investigated the influence of an intrathoracic procedure, esophagectomy, on IL-6 production in lung tissue. STUDY DESIGN: Fourteen paired lung tissue samples were obtained from patients before and after they underwent transthoracic esophagectomy for esophageal cancer. IL-6 levels in the lung were measured with enzyme-linked immunosorbent assay, and IL-6 mRNA expression was determined with real-time quantitative reverse transcription-polymerase chain reaction. Immunohistochemical staining was used to localize IL-6, and circulating levels were also measured. RESULTS: IL-6 protein and mRNA were significantly increased in lung tissue after this intrathoracic procedure (p < 0.05). Peak levels of plasma IL-6 after surgery were correlated with IL-6 levels in lung tissues obtained after the procedure (p < 0.05). Immunohistochemical staining revealed IL-6 production from alveolar and bronchial epithelial cells but not from alveolar macrophages. CONCLUSIONS: Transthoracic esophagectomy causes an increase in IL-6 production from airway epithelial cells, secondary to increased expression of IL-6 mRNA. Local response of lung tissue may be one source of increased serum IL-6 after this procedure.
Asunto(s)
Bronquios/química , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Interleucina-6/análisis , Pulmón/química , Alveolos Pulmonares/química , Mucosa Respiratoria/química , Anciano , Análisis de Varianza , Biopsia , Carcinoma de Células Escamosas/sangre , Ensayo de Inmunoadsorción Enzimática , Neoplasias Esofágicas/sangre , Femenino , Humanos , Inmunohistoquímica , Interleucina-6/sangre , Interleucina-6/genética , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , Factores de TiempoRESUMEN
OBJECTIVE: Our purpose was to investigate the effect of hormone replacement therapy on the postmenopausal changes in serum cytokine levels. STUDY DESIGN: Fifteen cytokines were measured by an enzyme-linked immunosorbent assay in 97 untreated and hormone replacement-treated women. Thirteen women were examined before and during hormone replacement therapy. RESULTS: Serum concentrations of macrophage colony-stimulating factor were significantly (P < .05) lower during the early postmenopausal period (< or = 10 years) than the values in premenopause and the elevated levels in the late postmenopausal period (< or = 30 years). A significant increase in tumor necrosis factor alpha and a decline in transforming growth factor beta1 were found in late postmenopausal women. Serum levels of macrophage colony-stimulating factor in women receiving hormone replacement therapy were significantly higher than those in untreated postmenopausal women. Furthermore, hormone replacement therapy induced a significant (P < .01) increase in serum levels of macrophage colony-stimulating factor, whereas serum levels of other cytokines were not affected. CONCLUSION: It is well documented that macrophage colony-stimulating factor lowers serum cholesterol concentrations and prevents atherosclerosis. Inducing the production of macrophage colony-stimulating factor is a possible additional mechanism of hormone replacement therapy in mediating the antiatherogenic effect.
Asunto(s)
Citocinas/sangre , Estrógenos Conjugados (USP)/uso terapéutico , Terapia de Reemplazo de Hormonas , Medroxiprogesterona/uso terapéutico , Posmenopausia/sangre , Adulto , Anciano , Anciano de 80 o más Años , Arteriosclerosis/prevención & control , Ensayo de Inmunoadsorción Enzimática , Estrógenos Conjugados (USP)/inmunología , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Humanos , Interferón gamma/sangre , Interleucinas/sangre , Linfotoxina-alfa/sangre , Factor Estimulante de Colonias de Macrófagos/sangre , Medroxiprogesterona/administración & dosificación , Medroxiprogesterona/inmunología , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/análisisRESUMEN
OBJECTIVE: To examine the levels of interleukin-18 (IL-18) bioactivity within the rheumatoid arthritis (RA) joint, and the differential effects of IL-12 and IL-18 on interferon-gamma (IFNgamma) production by T cell infiltrates. METHODS: Expression of IL-18 protein and messenger RNA (mRNA) was determined by enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction, respectively. The biologic activity of IL-18 was detected on the basis of IFNgamma secretion from IL-18-responding human myelomonocytic KG-1 cells. To determine the extent of inhibitory activity on binding of IL-18 to its receptor, a [125I]-IL-18 binding inhibition assay was performed, using a Chinese hamster ovary cell line transfected with a murine IL-18 receptor. RESULTS: The amount of IL-18 protein detected in both the serum and synovial fluid of RA patients was markedly larger than that detected in the serum and synovial fluid ofosteoarthritis (OA) patients, and serum IL-18 levels correlated with the levels of serum C-reactive protein. IFNgamma production by KG-1 cells was more strongly stimulated in synovial fluid samples from RA patients than in samples from OA patients, and this activity was largely diminished in the presence of anti-IL-18 antibody. In contrast, the activity of IL-18 binding inhibition in the serum and synovial fluid of RA patients was not significantly elevated compared with that in OA patients. RA synovial tissues showed increased expression of IL-18 mRNA and increased IL-18 protein synthesis compared with that in OA tissues. Purified CD14+ macrophages, but not activated fibroblast cell lines, from RA synovium were able to release mature IL-18, although both cell types expressed its transcripts. IL-18 alone showed a negligible effect on IFNgamma production by RA synovial tissue cells, in contrast to IL-12, which was directly stimulatory. However, IL-12-induced IFNgamma production was synergistically enhanced by IL-18, and yet was >50% reduced by neutralization of endogenous IL-18 with anti-IL-18 antibody. CONCLUSION: These results indicate that IL-18, produced predominantly by tissue macrophages, primarily potentiates IL-12-induced IFNgamma production by T cell infiltrates in RA synovium. Detection of significant IL-18 bioactivity in the joints, despite the presence of IL-18 binding inhibitors, supports an integral role of this cytokine in perpetuating the IFNgamma-dominant T cell cytokine response in RA.
Asunto(s)
Artritis Reumatoide/metabolismo , Interferón gamma/fisiología , Interleucina-18/metabolismo , Articulaciones/metabolismo , Formación de Anticuerpos/efectos de los fármacos , Humanos , Interferón gamma/biosíntesis , Interleucina-12/farmacología , Interleucina-18/sangre , Subunidad alfa del Receptor de Interleucina-18 , Osteoartritis/metabolismo , Receptores de Interleucina/antagonistas & inhibidores , Receptores de Interleucina-18 , Líquido Sinovial/química , Membrana Sinovial/citología , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
OBJECTIVES: In elderly subjects the capacity for antibody production is depressed. This immunosenescence state of humoral immunity is associated with the occurrence of autoimmune disorders involving CD5+ B (B-1) cells. Since estrogen is capable of stimulating the production of autoantibodies, this sex steroid hormone may be a contributing cause of the higher incidence of autoimmune diseases in women. In the present study, B cell subsets in women during the postmenopausal period was determined. The effect of hormone replacement therapy (HRT) on B cell subsets was examined to establish whether the administration of gonadal hormones influence humoral immunity in postmenopausal women. METHODS: Forty six untreated pre- and postmenopausal women and 39 women on HRT were studied. The proportion of B-1 (CD5+) and conventional CD5- B (B-2) lymphocytes was determined by two-color flow cytometry. Serum autoantibodies to a nuclear antigen and to interleukin (IL)-1alpha were measured by immunofluorescence and by radioimmunoassay, respectively. Thirteen women were examined prospectively before and during HRT. RESULTS: In late postmenopausal women (> or = 30 years postmenopausal period), the proportion of B-2 cells was significantly reduced (p<0.01) compared to those of premenopausal and perimenopausal women. HRT induced a significant (p<0.01) increase in the percentage of B-2 cells, while that of B-1 cells remained unchanged. HRT did not affect autoantibody production. CONCLUSION: HRT may retard the progress of immunosenescence by increasing the production of B-2 cells. Moreover, HRT appears not to increase the risk of autoimmune diseases developing in postmenopausal women.
Asunto(s)
Subgrupos de Linfocitos B/efectos de los fármacos , Terapia de Reemplazo de Hormonas , Posmenopausia , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estrógenos Conjugados (USP)/farmacología , Femenino , Humanos , Acetato de Medroxiprogesterona/farmacología , Persona de Mediana EdadRESUMEN
IL-18 is a novel cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. In the present study, we constructed plasmid vectors encoding the murine mature IL-18 cDNA linked with the Igkappa leader sequence and the pro-IL-18 cDNA to estimate the efficacy of the mature IL- 18 vector and to evaluate IL-18--producing tumor cells as a tumor vaccine. Colon 26 cells were transfected with the abovementioned vectors or with vector alone (mock). Reverse transcription-polymerase chain reaction analysis showed increased expression of murine IL-18 cDNA in both mature IL-18 and pro-IL-18 transfectants in comparison to that in mock transfected cells. The ability of the culture supernatants of mature IL-18 transfectants to induce IFN-gamma secretion was extremely high (40-140 pg/10(6) cells) in comparison to that of pro-IL-18 transfectants (4-18 pg/10(6) cells). When injected into syngeneic BALB/c mice, the growth of mature IL-18 transfectants, but not pro-IL-18 transfectants, was significantly less than that in mock transfected cells ( P< .01, by ANOVA and analysis of covariance). In addition, injection of colon 26 or Meth-A cells into mice immunized with a mature IL-18 transfectant revealed acquired immunity. Depletion of natural killer cells did not affect the growth of transfectants. However, the growth inhibitory effects were partially abrogated following treatment with anti-CD4+ and anti-CD8+ antibodies. These data suggest that the rejection of mature IL-18/colon 26 cells was mediated through T-cell activation. Gene therapy using mature IL-18 transfectants containing a plasmid vector and the Igkappa leader sequence may be a useful tumor vaccine.