Chronic intermittent hypoxia (CIH), a main feature of obstructive sleep apnoea (OSA), increases hypoxic ventilatory responses and elicits hypertension, partially attributed to an enhance carotid body (CB) responsiveness to hypoxia. As inflammation has been involved in CIHinduced hypertension and chemosensory potentiation, we tested whether ibuprofen may block CB chemosensory and cardiorespiratory alterations induced by CIH in a rat model of OSA.We studied the effects of ibuprofen (40 mg?kg -1 ?day -1 ) on immunohistochemical interleukin (IL)-1b and tumour necrosis factor (TNF)-a levels in the CB, the number of c-fos-positive neurons in the nucleus tractus solitarii (NTS), CB chemosensory and ventilatory responses to hypoxia, and arterial blood pressure in male rats either exposed for 21 days to 5% O 2 (12 episodes?h ) or kept under sham condition. CIH increased CB TNF-a and IL-1b and c-fos-positive neurons in the NTS, enhanced carotid chemosensory and ventilatory hypoxic responses, and produced hypertension. Ibuprofen prevented CB cytokine overexpression and CIH-induced increases in c-fos-positive neurons in the NTS, the enhanced hypoxic ventilatory responses and hypertension, but failed to impede the CB chemosensory potentiation.Results suggest that pro-inflammatory cytokines may contribute to the CIH-induced cardiorespiratory alterations, acting at several levels of the hypoxic chemoreflex and cardiovascular control pathways. KEYWORDS: Hypertension, hypoxia, inflammation, obstructive sleep apnoea O bstructive sleep apnoea (OSA) syndrome, a rising worldwide health problem, is characterised by chronic intermittent hypoxia (CIH), which is considered the main risk factor for developing hypertension and other cardiovascular diseases [1][2][3]. It has been proposed that oxidative stress, inflammation and sympathetic activation are involved in OSA-induced hypertension [3][4][5][6]. A growing body of evidence suggests that CIH enhances carotid body (CB) chemosensory responses to hypoxia contributing to the OSA-induced hypertension [6][7][8][9]. Indeed, OSA patients and animals exposed to CIH show potentiated ventilatory, sympathetic and cardiovascular responses to acute hypoxia [6][7][8][9][10]. Furthermore, recordings of carotid chemosensory discharges in situ and in vitro have shown that CIH selectively increases basal chemosensory discharges in normoxia and potentiates the chemosensory responses to acute hypoxia in rats and cats [9,[11][12][13].The repetitive episodes of hypoxia-reoxygenation during CIH exposure elicits oxidative stress due to the accumulation of reactive oxygen species (ROS), which are involved in the potentiation of the hypoxic CB chemosensory responses [9,11,13,14] and in the pathological consequences observed in animals exposed to CIH, and in OSA patients [3-5, 8, 9, 13]. Recently, we found that ascorbic acid supplementation, which impedes the systemic and local CB oxidative stress in the rat exposed to CIH for 21 days, prevented enhanced CB chemosensory and ventilatory responses to h...

Summary Streptococcus pneumoniae is a major aetiological agent of pneumonia worldwide, as well as otitis media, sinusitis, meningitis and sepsis. Recent reports have suggested that inflammation of lungs due to S. pneumoniae infection promotes bacterial dissemination and severe disease. However, the contribution of anti‐inflammatory molecules to the pathogenesis of S. pneumoniae remains unknown. To elucidate whether the production of the anti‐inflammatory cytokine interleukin‐10 (IL‐10) is beneficial or detrimental for the host during pneumococcal pneumonia, we performed S. pneumoniae infections in mice lacking IL‐10 (IL‐10−/− mice). The IL‐10−/− mice showed increased mortality, higher expression of pro‐inflammatory cytokines, and an exacerbated recruitment of neutrophils into the lungs after S. pneumoniae infection. However, IL‐10−/− mice showed significantly lower bacterial loads in lungs, spleen, brain and blood, when compared with mice that produced this cytokine. Our results support the notion that production of IL‐10 during S. pneumoniae infection modulates the expression of pro‐inflammatory cytokines and the infiltration of neutrophils into the lungs. This feature of IL‐10 is important to avoid excessive inflammation of tissues and to improve host survival, even though bacterial dissemination is less efficient in the absence of this cytokine.

SR-BI is the main receptor for high density lipoproteins (HDL) and mediates the bidirectional transport of lipids, such as cholesterol and vitamin E, between these particles and cells. During early development, SR-BI is expressed in extraembryonic tissueScavenger Receptor Class B type I (SR-BI) is the main receptor for high density lipoproteins (HDL), and numerous studies have described its role in mediating the bidirectional transport of lipids between these lipoproteins and cells 1 . In the liver, SR-BI is involved in the uptake of cholesterol from HDL and its excretion in bile, the final step in reverse cholesterol transport. SR-BI also participates in the uptake of cholesterol in steroidogenic tissues, such as the adrenal glands and ovaries, to be used as a substrate for steroid hormone synthesis 2 . Important information on the roles of SR-BI other than in cholesterol homeostasis and cholesterol provision for steroidogenesis, such as platelet aggregation, erythrocyte maturation and oocyte meiosis, has been generated from the SR-BI knock out (SR-BI −/− ) mouse since it was generated almost two decades ago 3 .In generating SR-BI −/− mice via heterozygous intercrosses, researchers noted that the proportion of weaned homozygous null mice was half that expected by the Mendelian ratio 3 . This evidence, together with the fact that SR-BI is present in murine trophoblasts involved in maternal-foetal nutrient exchange at different stages of gestation 4 , led researchers to postulate that this HDL receptor might be involved in embryonic development. We recently showed that nearly 50% of SR-BI −/− embryos fail to close the anterior neural tube and develop cranial NTD and exencephaly 5 , leading to perinatal death, which explains the deviation from the Mendelian ratio previously reported in weaned SR-BI null mice 3 . Among the spectrum of defective neurulation conditions conferred by abnormal closure at different portions of the neural tube, only cranial NTD is observed in SR-BI −/− embryos.During murine early development, SR-BI is not detected in the embryo itself but rather in trophoblast giant cells (TGC) from the parietal yolk sac 4,5 . TGC play a critical role in embryonic uptake of various nutrients from the maternal blood supply before the establishment of a mature placenta 6 . Despite the prominent role of SR-BI

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