Dendritic cell-derived nitric oxide is involved in IL-4-induced suppression of experimental allergic encephalomyelitis (EAE) in Lewis rats

Cytokines play a crucial role in initiating and perpetuating EAE, an animal model of multiple sclerosis (MS). A low dose of IL-4, administered by the nasal route over 5 days (100 ng/rat per day) prior to immunization, improved clinical scores of EAE induced in Lewis rats with myelin basic protein (MBP) peptide 68–86 (MBP 68–86). We examined whether dendritic cells (DC) may have contributed to the amelioration of the disease process. These professional antigen-presenting cells (APC) not only activate T cells, but also tolerize T cells to antigens, thereby minimizing autoimmune reactions. We found that IL-4 administration enhanced proliferation of DC. In comparison with DC of PBS-treated rats, DC from IL-4-treated rats secreted high levels of interferon-gamma (IFN-γ) and IL-10. Nitric oxide (NO) production by DC was also strongly augmented in IL-4-treated rats. In vitro studies showed that IL-4 stimulated DC expansion and that IFN-γ enhanced NO production by DC. DC-derived NO promoted apoptosis of autoreactive T cells. These results indicate that nasal administration of IL-4 promotes activation of DC and induces production of IFN-γ and IL-10 by DC. IL-10 suppresses antigen presentation by DC, while IFN-γ induces NO production by DC which leads to apoptosis in autoreactive T cells. Such a DC-derived negative feedback loop might contribute to the clinical improvement observed in EAE

Obstructive sleep apnea, metabolic syndrome, and age: will geriatricians be caught asleep on the job?

Obstructive sleep apnea (OSA) is increasingly recognized in older persons as an important cause of morbidity and mortality, resulting in cardiovascular disease, cognitive dysfunction, and disturbed sleep. It has been cited as an independent risk factor for the metabolic syndrome (MS). The elevated levels of cytokines, such as interleukin-6 and tumor necrosis factor-a, which also increase with age, are a common feature of both OSA and MS. Intermittent hypoxia caused by the recurring episodes of apnea and near-apnea in OSA is a major cause of its systemic effects. Mathematical models of OSA show how obesity and anatomic changes in the upper airways, which may be age-related, interact with the networks responsible for the chemical and neural control of breathing to cause the recurrent intermittent hypoxia of sleep apnea. Treatment of OSA with continuous positive airway pressure improves some aspects of the metabolic syndrome, reduces cardiovascular morbidity, and improves domains of cognitive function. OSA is more difficult to identify in the elderly because many of its symptoms can be caused by other disorders which are common in the elderly. Clinicians who encounter OSA may be advised to search for the presence of MS, and vice versa