Asunto(s)
Enfermedades Autoinmunes , Neutropenia , Rituximab , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/tratamiento farmacológico , Femenino , Francia , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Recuento de Leucocitos/métodos , Masculino , Persona de Mediana Edad , Neutropenia/tratamiento farmacológico , Neutropenia/etiología , Neutropenia/inmunología , Recurrencia , Retratamiento/estadística & datos numéricos , Estudios Retrospectivos , Rituximab/administración & dosificación , Rituximab/efectos adversos , Resultado del TratamientoRESUMEN
Sjögren syndrome (SS) is an autoimmune disease characterized by chronic inflammatory infiltrates in the salivary and lacrimal glands. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T-cells, predominantly found in mucosal tissues with crucial role in epithelial homeostasis. Thus, MAIT cells may be implicated in mucosal alterations of SS patients. Activation markers, inflammatory and cytotoxic cytokines were examined in 23 SS patients and compared to 23 healthy controls (HC). Tissular MAIT cells in salivary gland (SG) biopsies were also analyzed. Circulating MAIT cells were decreased in SS patients with a higher expression of CD69 and a higher CD4/CD8 ratio of MAIT cells. MAIT cells showed a higher production of IFNγ, TNFα and GzB in SS compare to HC. Tissular MAIT cells were present within inflamed SG of SS patients, while they were absent in SG of HC. Overall, circulating MAIT cells are decreased in the peripheral blood of SS albeit producing higher amounts of IFNγ, TNFα, and GzB. Tissular MAIT cells are detected in salivary glands from SS with a proinflammatory tissular cytokine environment. MAIT cells with abnormal phenotype, functions and tissular homeostasis may contribute to epithelial damage in SS.
Asunto(s)
Células T Invariantes Asociadas a Mucosa , Glándulas Salivales , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/patología , Células T Invariantes Asociadas a Mucosa/inmunología , Células T Invariantes Asociadas a Mucosa/metabolismo , Femenino , Persona de Mediana Edad , Masculino , Glándulas Salivales/patología , Glándulas Salivales/inmunología , Glándulas Salivales/metabolismo , Adulto , Citocinas/metabolismo , Anciano , Estudios de Casos y ControlesRESUMEN
Concomitant administration of multiple drugs frequently causes severe pharmacokinetic or pharmacodynamic drug-drug interactions (DDIs) resulting in the possibility of enhanced toxicity and/or treatment failure. The activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), a drug efflux pump sharing localization and substrate affinities with CYP3A4, is a critical determinant of drug clearance, interindividual variability in drug disposition and clinical efficacy, and appears to be involved in the mechanism of numerous clinically relevant DDIs, including those involving dexamethasone. The recent increase in the use of high doses of dexamethasone during the COVID-19 pandemic have emphasized the need for better knowledge of the clinical significance of drug-drug interactions involving dexamethasone in the clinical setting. We therefore aimed to review the already published evidence for various DDIs involving dexamethasone in vitro in cell culture systems and in vivo in animal models and humans.