Interleukin 33 (IL-33) is an alarmin cytokine from the IL-1 family. IL-33 is localized in the nucleus and acts there as a gene regulator. Following injury, stress or cell death, it is released from the nucleus, and exerts its pro-inflammatory biological functions via the transmembrane form of the ST2 receptor, which is present mainly as attached to immune cells. In recent years, IL-33 became a focus of many studies due to its possible role in inflammatory disorders. Among respiratory disorders, the contribution of IL-33 to the development of asthma, in particular, has been most identified. Increased level of IL-33 in lung epithelial cells and blood serum has been observed in asthma patients. The IL-33/ST2 interaction activated the Th2 mediated immune response and further production of many pro-inflammatory cytokines. Single nucleotide polymorphisms in the IL-33 gene cause a predisposition to the development of asthma. Similarly, in chronic pulmonary obstructive disease (COPD), both increased expression of IL-33 and the ST2 receptor has been observed. Interestingly, cigarette smoke, a key inducer of COPD, not only activates IL-33 production by epithelial and endothelial cells, but also induces the expression of IL-33 in peripheral blood mononuclear cells. Knowledge regarding its contribution in other respiratory disorders, such as obstructive sleep apnea, remains greatly limited. Recently it was shown that IL-33 is one of the inflammatory mediators by which levels in blood serum are increased in OSA patients, compared to healthy control patients. This mini review summarizes current knowledge on IL-33 involvement in chosen chronic respiratory disorders and proposes this interleukin as a possible link in the pathogenesis of these diseases.

Obstructive sleep apnea is a chronic condition characterized by recurrent episodes of apneas or hypopneas during sleep leading to intermittent hypoxemia and arousals. The prevalence of the sleep disordered breathing is estimated that almost 50% of men and 24% of women suffer from moderate to severe form of the disorder. Snoring, collapse of upper airways and intermittent hypoxia are main causes of smoldering systemic inflammation in patients suffering from obstructive sleep apnea. The systematic inflammation is considered one of the key mechanisms leading to significant cardiovascular complications. Blood platelets, formerly not even recognized as cells, are currently gaining attention as crucial players in the immune continuum. Platelet surface is endowed with receptors characteristic for cells classically belonging to the immune system, which enables them to recognize pathogens, immune complexes, and interact in a homo- and heterotypic aggregates. Platelets participate in the process of transcellular production of bioactive lipids by delivering both specific enzymes and substrate molecules. Despite their lack of nucleus, platelets synthetize proteins in a stimuli-dependent manner. Atherosclerosis and consequent cardiovascular complications result from disruption in homeostasis of both of the platelet roles: blood coagulation and inflammatory processes modulation. Platelet parameters, routinely evaluated as a part of complete blood count test, were proposed as markers of cardiovascular comorbidity in patients with obstructive sleep apnea. Platelets were found to be excessively activated in this group of patients, especially in obese subjects. Persistent activation results in enhanced spontaneous aggregability and change in cytokine production. Platelet-lymphocyte ratio was suggested as an independent marker for cardiovascular disease in obstructive sleep apnea syndrome and continuous positive air pressure therapy was found to have an impact on platelet parameters and phenotype. In this literature review we summarize the current knowledge on the subject of platelets involvement in obstructive sleep apnea syndrome and consider the possible pathways in which they contribute to cardiovascular comorbidity.

Obstructive sleep apnea syndrome (OSA) is described as an independent risk factor for the onset and progression of type 2 diabetes (T2DM), as well as for insulin resistance (IR). The mechanisms underlying these processes remain unclear. One of the proposed molecular mechanism is based on the oxygen-sensitive α-subunit of hypoxia-inducible factor 1 (HIF-1α)-a key regulator of oxygen metabolism. The concept that stabilization of HIF-1α may influence T2DM and IR is supported by cell and animal models. Cell culture studies revealed that both glucose uptake and glycolysis are regulated by HIF-1α. Furthermore, animal models indicated that increased fasting glucose may be caused by a single night with intermittent hypoxia. Moreover, in these models, hypoxia time was correlated with IR. Mice models revealed that inhibition of HIF-1α protein may downregulate fasting blood glucose and plasma insulin level. Administration of superoxide dismutase mimetic resulted in inhibition of HIF-1α protein, catecholamines, and chronic intermittent hypoxia-induced hypertension in a mice model. The hypothesis that hypoxia is an independent risk factor for IR is strengthened by experimentally confirmed improvement of insulin sensitivity among OSA patients treated with the continuous positive airway pressure. Furthermore, recent studies suggest that HIF-1α protein concentration is increased in individuals with OSA. In this literature review, we summarize the current knowledge about HIF-1α in OSA in relation to the possible pathways in which they contribute to metabolic disorders.

Our data suggest that the informative value of sleep reference data in healthy individuals is limited because of high interindividual and intraindividual variation within sleep variables. More research, preferably in the form of meta-analyses and/or large international databases, is needed to further investigate the relevance of such reference data for mental and physical health. In the absence of such knowledge, giving patients feedback about deviations from the norm in their sleep profile may give rise to ill-founded concerns and worry.