Asunto(s)
Vías Clínicas/tendencias , Prestación Integrada de Atención de Salud/tendencias , Granulomatosis con Poliangitis/terapia , Hipertensión/terapia , Medicina Interna/tendencias , Predicción , Alemania , Granulomatosis con Poliangitis/diagnóstico , Humanos , Hipertensión/diagnóstico , Modelos OrganizacionalesRESUMEN
The bactericidal/permeability-increasing protein (BPI) is an endotoxin-binding neutrophil leukocyte-granule protein with antibacterial and anti-endotoxin properties. A recombinant form of BPI (rBPI21) has been developed and is being tested as a therapeutic agent to treat gram-negative bacterial infections and exposure to gram-negative bacterial endotoxin. BPI is also a target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA). BPI-ANCA are present in cystic fibrosis, inflammatory bowel disease, vasculitis, and primary sclerosing cholangitis; presence of BPI-ANCA appears associated with a higher inflammatory disease activity and greater organ damage. BPI-ANCA as well as ANCA directed at other neutrophil-granule proteins may exacerbate inflammation by nonspecific effects of extracellular and cell-associated immune complexes. BPI-ANCA may further worsen inflammation by reducing the ability of BPI to promote clearance of gram-negative bacteria and bacterial-associated endotoxin.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Autoantígenos/inmunología , Proteínas Sanguíneas/inmunología , Proteínas de la Membrana , Adulto , Animales , Especificidad de Anticuerpos , Péptidos Catiónicos Antimicrobianos , Enfermedades Autoinmunes/inmunología , Proteínas Sanguíneas/química , Niño , Preescolar , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Citocinas/metabolismo , Gránulos Citoplasmáticos/química , Evaluación Preclínica de Medicamentos , Endotoxinas/metabolismo , Eosinófilos/metabolismo , Predicción , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Lactante , Inflamación/inmunología , Ratones , Estudios Multicéntricos como Asunto , Neutrófilos/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/uso terapéutico , Vasculitis/inmunologíaRESUMEN
Immuno-augmentation with substances of bacterial origin was studied in vitro for its ability to induce polyclonal B-cell activation. Biostim, Broncho-Vaxom, Omnadin, Paspat and OK 432 were compared for their B-cell mitogenicity with classical polyclonal B-cell activators (Staph. aureus Cowan I, KlebsM, Pokeweed mitogen). B-cell mitogenicity, as measured by 3H-thymidine incorporation into proliferating blood B-cells, was not induced by any of the studied preparations. On the other hand, OK 432 produced a T-cell dependent and Biostim a T-cell independent blood B-cell differentiation in immunoglobulin producing cells. However, the extent of immunoglobulin production was clearly less than with the polyclonal B-cell activator KlebsM. These results demonstrate that, in some of the preparations, in vivo polyclonal B-cell activation can be expected to occur.