Introduction
Inflammation in OSAS
Biomarkers of Inflammation
Reference | Number of subjects | Detecting parameter | Cytokines levels alteration | Cytokines concentrations correlated with |
---|---|---|---|---|
Nadeem et al. 2013 [33] | Meta-analysis of 2952 OSAS and 2784 controls | CRP, TNF-α, IL-6, IL-8, ICAM, VCAM, and selectins | CRP↑, TNF-α↑, IL-6↑, IL-8↑, ICAM↑, VCAM↑, and selectins↑ | Age, BMI, AHI |
Bouloukaki et al. 2017 [34] | 858 OSAS; 190 controls | CRP, fibrinogen, UA and ESR | CRP↑, fibrinogen↑, UA↑ | Gender, BMI, AHI, ODI and mean and minimum SaO2, TST90 and active somking |
Bozic et al. 2018 [35] | 50 OSAS; 25 controls | TNF-α, IL-6 and hsCRP | TNF-α↑, IL-6↑, hsCRP↑ | Plasma adropin levels |
Motamedi et al. 2018 [36] | 50 OSAS; 24 controls | Tau, IL-6, IL-10, CRP, TNF-α and Aβ | Tau↑, IL-6↑ | AHI |
Svatikova et al. 2003 [37] | 20 OSAS; 17 controls | SAA | SAA↑ | AHI |
Sozer et al. 2018 [38] | 60 OSAS; 24 controls | CRP, PTX-3, ProCT, IL-33 and sST2 | PTX-3↑, IL-33↑, and sST2↑ | BMI, ODI, minimum SaO2 |
Inflammation Levels after CPAP treatment
Reference | Number of patients | Treatment duration | Daily duration | Detecting parameter | Before treatment | After treatment |
---|---|---|---|---|---|---|
Schiza et al. 2010 [60] | 528 | 12 months | ≥ 4 h/night | CRP | CRP↑ | CRP↓ |
Steiropoulos et al. 2009 [61] | 52 | 6 months | ≥ 4 h/night | TNF-α, IL-6, UA and CD4+ cell count | TNF-α↑ UA↑ CD4+ cell count↑ | TNF-α↓ UA↓ CD4+ cell count↓ |
Yokoe et al. 2003 [62] | 30 | 1 month | NA | CRP, IL-6 | CRP↑ IL-6↑ | CRP↓ IL-6↓ |
Jin et al. 2017 [63] | 100 | 3 months | NA | IL-8, TNF-α, CRP, ICAM-1, VCAM-1, and selectin | IL-8↑ TNF-α↑ CRP↑ ICAM-1↑ VCAM-1↑ selectin↑ | IL-8↓ TNF-α↓ CRP↓↓ ICAM-1↓ VCAM-1↓ selectin↓ |
Wu et al. 2010 [64] | 30 | 2 months | NA | HMGB1 and NOx | HMGB1↑ NOx ↓ | HMGB1↓ NOx↑ |
Kuramoto et al. 2009 [65] | 116 | 3 months | NA | SAA, CRP | CRP↑ SSA↑ | SAA↓ |
Ohga et al. 2003 [66] | 20 | 8–18 months | NA | ICAM-1, IL-8, MCP-1 | ICAN-1↑ IL-8↑ MCP-1↑ | ICAM-1↓ IL-8↓ |
Lu et al. 2017 [67] | 58 | 2 months | NA | NF-κB, HIF-1α and SPD | NF-κB↑ HIF-1α↑ SPD↓ | SPD↑ NF-κB↓ HIF-1α↓ |
Tichanon et al. 2016 [68] | 13 | 3 months | ≥ 5 h/night | FeNO, MDA | FeNO↑ MDA↑ | FeNO↓ MDA↓ |
Mechanisms of Inflammation in OSAS
Cognitive impairment in OSAS
Brain tissue damage and neurocognitive dysfunction in OSAS
Relationship between cognitive dysfunction and OSAS
Role of inflammation in the development of cognitive dysfunction in OSAS
Association of inflammation and cognitive dysfunction in OSAS patients
Inflammation leading to cognitive deficits in CIH animals
Reference | Experiment animal | Control animal | Detecting parameter | Cognitive dysfunction | Results |
---|---|---|---|---|---|
Dong et al. 2018 [135] | V + CIH; SEV + CIH | V + RA; SEV + RA | TNF-α, IL-1β, activity of microglia, and expression and activity of PPAR-γ in hippocampus | Impaired spatial learning and memory in experiment group. SEV exaggerated the cognitive deficits | V + CIH showing increased TNF-α, IL-1β levels and microglia activity. SEV aggravated microglia-mediated inflammation via downregulation of PPAR-γ |
Sapin et al. 2015 [136] | C57BL/6J mice + IH | C57BL/6J mice + RA | CCL5, MCP-1/CCL2, ICAM-1, TNF-α, IL-1β, IL-6 and IL-10 mRNA and microglial changes in the dH and vH regions of hippocampus | NA | Experiment group showing increased density and morphological features of microglia priming in dH; IL-1β and RANTES/CCL5 mRNA increased in dH of experiment group |
Shi et al. 2018 [137] | C57BL/6J mice + IH; T2DM + IH | C57BL/6J mice + RA; T2DM + RA | Hippocampal neurons apoptosis, microglia activity, HMGB1, NF-κB-p65, TNF-α and IL-1β | Longer escape latency; Reduced numbers of platform crossing and percentage of time spent in the fourth quadrant in Morris water maze of experiment group | All the parameters were significantly increased in experiment group |
Snyder et al. 2017 [138] | Adult male rats + CIH | Adult male rats + RA | IL-4, IL-5, IL-6, IL-10, IL-13, TNF-α and IFN-γ protein levels and OS levels in brain tissue | NA | Exposure to CIH increases inflammation and OS levels in brain regions associated with neurodegenerative diseases |
Darnall et al. 2017 [139] | Rat pups + CIH | Rat pups + RA | Gro/CXCL1 in plasma; IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO and TNF-α in brain tissue and NSE | NA | Increased plasma levels of Gro/CXCL1, cerebellar levels of IFN-γ and IL-1β and NSE in rat pups + CIH |
Kim et al. 2013 [140] | ALS + CIH; Wt-CIH | ALS + RA; Wt-RA | NF-κB inhibitor alpha, 4-HNE, anti-GFAP and motor neuron counts | Impaired spatial memory in mice exposed to CIH | ALS + CIH showing poor motor learning and spatial memory, higher levels of OS and inflammation and elevated motor neuron death |
Block et al. 2003 [141] | Adult rats + IH | Adult rats + RA | Gene expression of TLR4 and mRNA levels of iNOS, COX-2, TNF-α, IL-1β and IL-6 in microglia | NA | All the parameters showing increase in IH group |
Deng et al. 2015 [142] | V + CIH; atorvastatin + CIH | V + RA; atorvastatin + RA | TNF-α, IL-1β, MDA, SOD; expression of TLR4, MyD88 and TRIF mRNA and protein; neuronal cell damage in hippocampus CA1 region | NA | All parameters except SOD were increased in V + CIH mice. V + CIH showing lower SOD level. Atorvastatin attenuated all these changes |
Burckhardt et al. 2008 [143] | V + IH; GTP + IH | V + RA; GTP + RA | PGE2, RAGE, the ratio of RAGE/β-actin, GFAP, MDA, and p47phox in brain tissue | GTP attenuated IH-induced spatial learning deficits | All parameters were significantly increased in brain tissue of experiment group. GTP alleviated the IH induced inflammation and OS in the brain |
Lam et al. 2015 [144] | V + CIH; LBPs + CIH | V + RA; LBPs + RA | TNF-α, IL-1β, COX-2, NFκB, MDA, antioxidant enzymes (SOD, GPx-1), ER stress and apoptosis in the hippocampus | LBPs reversed CIH-induced spatial memory deficits | V + CIH showing increased levels of TNF-α, IL-1β, COX-2, NFκB, ER stress, OS and neuronal apoptosis in hippocampus. LBPs decreased inflammation and OS levels and improved cognitive deficits |
Deng et al. 2015 [145] | V + CIH; BBG + CIH | V + RA; BBG + RA | P2X7R mRNA and protein, NFκB, TNF-α, IL-β, IL-6, IL-18, NOX2, SOD, MDA in the hippocampus | BBG improved spatial learning performance in mice exposed to CIH | All parameters showing highest increases in the hippocampus of V + CIH; BBG alleviated CIH induced inflammation, OS, neural injury and cognition deficits |
Yuan et al. 2015 [146] | V + CIH; Telmisartan + CIH | V + RA; Telmisartan + RA | Plasma CRP and IL-6; MDA, NOS, NO and apoptosis in hippocampal CA1 region | NA | All parameters showing highest increases in V + CIH. Telmisartan decreased inflammation and OS levels and hippocampal apoptosis |
Row et al. 2004 [147] | PAFR–/– mice + IH; Wt + IH | PAFR–/– mice +RA; Wt +RA | NOS activity, COX-2 and PGE2 in cortical; caspase 3 in cortex and CA1 region of hippocampus | Impaired spatial learning showing in Wt + IH but not PAFR–/– mice + IH | Wt + IH showing the highest levels of all the parameters. PAFR–/– alleviated neuroinflammation and apoptosis in the brain |