Because of their unique capacity to cross-present Ags to CD8+ T cells, mouse lymphoid tissue–resident CD8+ dendritic cells (DCs) and their migratory counterparts are critical for priming antiviral T cell responses. High expression of the dsRNA sensor TLR3 is a distinctive feature of these cross-presenting DC subsets. TLR3 engagement in CD8+ DCs promotes cross-presentation and the acquisition of effector functions required for driving antiviral T cell responses. In this study, we performed a comprehensive analysis of the TLR3-induced antiviral program and cell-autonomous immunity in CD8+ DC lines and primary CD8+ DCs. We found that TLR3-ligand polyinosinic-polycytidylic acid and human rhinovirus infection induced a potent antiviral protection against Sendai and vesicular stomatitis virus in a TLR3 and type I IFN receptor–dependent manner. Polyinosinic-polycytidylic acid–induced antiviral genes were identified by mass spectrometry–based proteomics and transcriptomics in the CD8+ DC line. Nanostring nCounter experiments confirmed that these antiviral genes were induced by TLR3 engagement in primary CD8+ DCs, and indicated that many are secondary TLR3-response genes requiring autocrine IFN-β stimulation. TLR3-activation thus establishes a type I IFN–dependent antiviral program in a DC subtype playing crucial roles in priming adaptive antiviral immune responses. This mechanism is likely to shield the priming of antiviral responses against inhibition or abrogation by the viral infection. It could be particularly relevant for viruses detected mainly by TLR3, which may not trigger type I IFN production by DCs that lack TLR3, such as plasmacytoid DCs or CD8− DCs.
Hiccups are a rare but potentially debilitating side effect of opioid treatment, with only a handful of reported cases in the medical literature. the pathophysiological mechanism linking opioids and hiccups is unknown, and a lack of evidence exists concerning the optimal management of the condition. We report on a 64-year-old man diagnosed with advanced renal cancer and painful osteolytic metastases, presenting persistent hiccups while on opioid treatment. Hiccups recurred after multiple challenges with codeine, morphine and hydromorphone on separate occasions. Hiccups ceased only after opioid discontinuation, although various pharmacological treatments were tried to shorten the duration of hiccups. eventually, fentanyl was introduced and was well tolerated by the patient, without any recurrence of hiccups. the chronological correlation between opioid initiation and the onset of hiccups, as well as opioid discontinuation and the termination of hiccups leads to the conclusion that a causal role of codeine, morphine and hydromorphone in this occurrence is likely. Individual susceptibility probably plays a central role in the development of opioid-related hiccups. opioid rotation is a promising strategy in the management of opioid-related hiccups, particularly when the mere discontinuation of the opioid is not a viable option, such as in the oncology and palliative care field.
Prescription des opiacés en médecine de premier recours : le cas des douleurs chroniques non cancéreuses La douleur, dont la douleur chronique non cancéreuse (DCNC), est un motif de consultation très fréquent en médecine de premier recours. La DCNC regroupe des populations hétérogènes de patients dont la prise en charge est généralement complexe. L'augmentation de la prescription d'opiacés en Suisse et dans le monde concerne davantage les DCNC, alors que l'utilisation d'opiacés pour cette indication est controversée. Différentes études suggèrent que les effets bénéfiques sur la douleur et la fonctionnalité seraient limités contrairement aux effets secondaires relativement fréquents. Cet article a pour but de résumer l'état des connaissances sur la prescription d'opiacés pour les DCNC et les recommandations internationales pour fournir une aide pratique en médecine générale. Opiod prescription in primary care: the case of chronic non cancer painPain, including chronic non-cancer pain (CNCP), is a common reason for primary care consultation. CNCP encompasses a heterogeneous group of patients, whose care is often complex. The increase in opioid prescription in Switzerland and worldwide is associated with CNCP, while opioid use for this indication is debated. Several studies suggest a limited effect on pain and function, while adverse effects are frequent. This article aims to summarize what is known about opioid prescription for CNCP and international guidelines and highlight important aspects for the general practitioner.
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