RESUMO
Th17 cells have been implicated in a number of inflammatory and autoimmune diseases. The phospholipid mediator platelet-activating factor (PAF) is found in increased concentrations in inflammatory lesions and has been shown to induce IL-6 production. We investigated whether PAF could affect the development of Th17 cells. Picomolar concentrations of PAF induced IL-23, IL-6, and IL-1ß expression in monocyte-derived Langerhans cells (LCs) and in keratinocytes. Moreover, when LC were pretreated with PAF and then cocultured with anti-CD3- and anti-CD28-activated T cells, the latter developed a Th17 phenotype, with a significant increase in the expression of the transcriptional regulator RORγt and enhanced expression of IL-17, IL-21, and IL-22. PAF-induced Th17 development was prevented by the PAF receptor antagonist WEB2086 and by neutralizing antibodies to IL-23 and IL-6R. This may constitute a previously unknown stimulus for the development and persistence of inflammatory processes that could be amenable to pharmacologic intervention.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Fator de Ativação de Plaquetas/farmacologia , Células Th17/citologia , Células Th17/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Citometria de Fluxo , Humanos , Interleucina-1beta/metabolismo , Interleucina-23/metabolismo , Interleucina-6/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Células Th17/metabolismoAssuntos
Antibacterianos/efeitos adversos , Cefalosporinas/efeitos adversos , Exantema/induzido quimicamente , Dermatopatias Vesiculobolhosas/induzido quimicamente , Doença Aguda , Animais , Antibacterianos/administração & dosagem , Biópsia , Cefalosporinas/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Pele/patologia , Picada de Aranha/tratamento farmacológico , Volume Sistólico , Síndrome de Resposta Inflamatória Sistêmica/induzido quimicamente , Taquicardia Sinusal/induzido quimicamente , CefprozilRESUMO
UNLABELLED: AbstractBackground:Calciphylaxis is a life-threatening condition traditionally observed in patients with end-stage renal disease. Cases of nonuremic calciphylaxis have also been reported, but data on this rare condition are mainly empirical. OBJECTIVES: To present a case of severe nonuremic calciphylaxis treated with intravenous sodium thiosulfate (IV STS) and to assess the implications of this treatment. METHODS: Case report and review of the literature. RESULTS: A nonuremic patient diagnosed with distal calciphylaxis was started on IV STS after a 12-month nonresponse to conventional therapy. On week 12, the patient requested palliative care, given her many side effects (transient severe nausea and significant electrolyte imbalance). Pain subsided after 14 weeks, and complete wound healing was observed after 6 months. CONCLUSION: Based on this case report, IV STS can improve refractory calciphylaxis in nonuremic patients. However, literature on the subject remains scarce. Careful monitoring for adverse transient side effects is advised.