RESUMEN
Whether and when auto-reactivity after stroke occurs is still a matter of debate. By using overlapping 15mer peptide pools consisting of myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) we show increased frequencies of immunodominant MOG- and MBP T cell responses in acute ischemic stroke which were associated with reduced frequencies of naïve T cells as well as CD8+ TEMRA cells. Auto-reactive CNS antigen-specific T cells responses as well as alterations of T cell subpopulations normalized in long-term follow up after stroke. Our findings suggest that stroke-induced immunodepression might function as an adaptive mechanism in order to inhibit harmful and long-lasting CNS antigen-specific immune responses.
Asunto(s)
Autoinmunidad , Isquemia Encefálica/inmunología , Memoria Inmunológica , Accidente Cerebrovascular/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/terapia , Ensayo de Immunospot Ligado a Enzimas , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Interferón gamma/metabolismo , Masculino , Persona de Mediana Edad , Proteína Básica de Mielina/metabolismo , Glicoproteína Mielina-Oligodendrócito/metabolismo , Neuroinmunomodulación , Accidente Cerebrovascular/terapiaRESUMEN
The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally administered etoricoxib and to compare it with effect data, i.e., COX-2-inhibition in patients after hip surgery. The study was performed in a blinded, randomized, parallel group design. A total of 12 adult patients were included who received 120 mg etoricoxib (n = 8) or placebo (n = 4) on day 1 post-surgery. Samples from plasma, CSF, and tissue exudates were collected over a period of 24 h post-dosing and analyzed for etoricoxib and prostaglandin E(2) (PGE(2)) using liquid chromatography-tandem mass spectrometry and immuno-assay techniques. CSF area under the curve (AUC) [AUCs((O-24h))] for etoricoxib amounted to about 5% of the total AUC in plasma (range: 2-7%). Individual CSF lag times with respect to (50%) peak plasma concentration were
