RESUMEN
Interleukin 18 (IL-18) is a potent proinflammatory cytokine involved in the host defence by upregulating both innate and acquired immune responses and may be of particular importance also in mechanisms of kidney allograft rejection. Immunohistochemical staining of protocol biopsies showed constitutive IL-18 expression in the epithelium of distal tubules with the induction of immunoreactivity in acute rejection patients where also proximal tubules, infiltrating leukocytes, and endothelium were strongly positive. Furthermore, serum levels of IL-18 were significantly elevated in patients with acute rejection of kidney allograft (1247+/-389 pg/l) as compared to patients with uncomplicated outcome of kidney transplantation (444+/-164 pg/l) and subjects with acute tubulointerstitial nephropathy (385+/-155 pg/l, p<0.0001 for both comparisons). Tissue culture model of renal epithelial cells expressed IL-18 mRNA constitutively and released mature IL-18 in response to TNF-alpha and IFN-gamma. We assume that upregulation of epithelial IL-18 plays an important role in immune and immunopathological reactions in renal parenchyma and contributes to rejection mechanisms of kidney allograft.
Asunto(s)
Rechazo de Injerto/genética , Interleucina-18/metabolismo , Trasplante de Riñón , Regulación hacia Arriba , Biopsia , Línea Celular , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Humanos , Inmunohistoquímica , Interferón gamma/farmacología , Interleucina-18/genética , Riñón/metabolismo , Riñón/patología , Riñón/cirugía , ARN/genética , Trasplante HomólogoRESUMEN
IL-18 is a multifunctional cytokine that augments both innate and acquired immunity and potentiates Th1 and Th2 reactions. We studied the expression of IL-18 receptor (IL-18R) on renal and respiratory epithelial cell lines. Both cell lines upregulated IL-18R mRNA and IL-18R membrane expression in response to TNF alpha and other proinflammatory cytokines. The function of IL-18R was confirmed by induction of IL-8 release from epithelial cells in response to recombinant IL-18. Epithelial cells may represent an important target for IL-18, mainly under inflammatory conditions associated with TNF alpha release.
Asunto(s)
Células Epiteliales/efectos de los fármacos , Receptores de Interleucina/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Regulación hacia Arriba/efectos de los fármacos , Línea Celular Tumoral , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Interleucina-18/genética , Interleucina-18/farmacología , Subunidad alfa del Receptor de Interleucina-18 , Interleucina-8/metabolismo , Receptores de Interleucina-18 , Proteínas Recombinantes/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
We have investigated the association between the presence of antibodies to HLA class II antigens and the development of acute and chronic rejection after kidney transplantation. Sera from seventy-one patients before, shortly (2 weeks), and in the period between 8 and 22 months after transplantation were analyzed by the standard complement-dependent cytotoxicity (CDC) test, ELISA-LATM, and LAT tests. Absence of antibodies to HLA class II antigens before and shortly after transplantation was associated with a lower incidence of rejection episodes in the first post-transplant year. Donor-specific class II antibodies could not be detected by the ELISA-LAT test and there was no statistically significant difference in serum creatinine levels between the antibody-positive and antibody-negative patient groups two years after transplantation. Our study suggests that anti-HLA class II antibodies represent a risk factor for the development of acute immunological complications during the first year after transplantation.
Asunto(s)
Anticuerpos/sangre , Rechazo de Injerto/etiología , Antígenos de Histocompatibilidad Clase II/inmunología , Trasplante de Riñón , Enfermedad Aguda , Adulto , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Análisis de Supervivencia , Trasplante HomólogoRESUMEN
Recent literary data suggest that antibodies to HLA antigens undetectable by the standard complement-dependent cytotoxicity test may cause not only chronic, but also acute immunological complications after kidney transplantation. The aim of this study was to investigate the significance of non-cytotoxic antibodies to HLA antigens for the development of immunological complications and a worse graft prognosis after first kidney transplantation. Sera before and early after transplantation from 120 first kidney recipients were analyzed by flow cytometry (FCXM), ELISA and the standard complement-dependent cytotoxicity (CDC) test. Pre-transplant FCXM negativity was related to a lower incidence of rejection episodes in the first post-transplant year ( P<0.01). A significant association between acute rejection and the presence of antibodies to HLA class II antigens before and after transplantation was also found ( P<0.05). Our study supports the findings of other centers of the detrimental role to the kidney graft played by anti-HLA antibodies undetectable by the classical CDC test.