Salivary Cytokines and Airways Disease Severity in Patients with Cystic Fibrosis

Abstract

About 50% of patients with cystic fibrosis (CF) have sinonasal complications, which include inferior turbinate hypertrophy (NTH) and/or nasal polyposis (NP), and different degrees of lung disease, which represents the main cause of mortality. Monitoring of sinonasal disease requires complex instrumental procedures, while monitoring of lung inflammation requires invasive collection of bronchoalveolar lavage fluid. The aim of this study was to investigate the associations between salivary cytokines levels and CF-related airway diseases. Salivary biochemical parameters and cytokines, i.e., interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-α), were analyzed in resting saliva from healthy subjects and patients with CF. Patients with CF showed significantly higher levels of salivary chloride, IL-6, IL-8, and TNF-α and lower calcium levels than healthy subjects. Among patients with CF, IL-6 and IL-8 were significantly higher in patients with NTH, while TNF-α was significantly lower in patients with NP. A decreasing trend of TNF-α in patients with severe lung disease was also observed. On the other hand, we did not find significant correlation between cytokine levels and Pseudomonas aeruginosa or Stenotrophomonas maltophilia colonization. These preliminary results suggest that salivary IL-6 and IL-8 levels increase during the acute phase of sinonasal disease (i.e., NTH), while the end stages of pulmonary disease and sinonasal disease (i.e., NP) show decreased TNF-α levels.

The Challenges of OSCC Diagnosis: Salivary Cytokines as Potential Biomarkers

“…The studies that targeted salivary cytokines as OSCC biomarkers reported a strong relationship between their high levels and the presence of OSCC [ 18 , 49 , 51 , 53 , 54 , 55 , 56 , 57 , 60 , 61 , 62 , 63 , 64 ]. Further challenges consist in ruling out other possible causes that could determine the increase of salivary cytokines, such as periodontitis, cystic fibrosis, Sjögren’s syndrome, and acute stress [ 13 , 19 , 71 , 72 ]. Taking these facts into consideration, besides an oral cancer screening tool that utilizes cytokine biomarkers, it is important to evaluate general health and oral statuses.…”

“…Several studies have shown that the changes determined by OSCC may be detected in saliva at the genomic, transcriptomic, and proteomic levels [ 11 ]. Also, recent proteomic studies of saliva provided new information that correlates salivary proteins/peptides in general and cytokines in particular with various pathological states [ 12 , 13 , 14 , 15 , 16 ]. The study performed by Kosaka et al [ 14 ] mentions a strong relationship between the increased interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels and the incidence of atherosclerosis found in their study group [ 14 ].…”

“…Another focus was upon the existing association of different salivary cytokine levels and the severity of cystic fibrosis airway disease. Cataldo et al [ 13 ] outlined in their results that an increase of salivary IL-8, IL-6, and TNF-α was identified in the cystic fibrosis group compared to the controls.…”

Cystic Fibrosis-Screening Positive Inconclusive Diagnosis: Newborn Screening and Long-Term Follow-Up Permits to Early Identify Patients with CFTR-Related Disorders

“…The evaluation of the liver status and the presence of CF liver disease (CFLD) were evaluated on the basis of clinical, biochemical and U/S scanning (if necessary) results. The evaluation of sinonasal pathology was performed by clinical evaluation followed by rhinoscopy and, if necessary, by TC scanning, as described [ 18 ]. Furthermore, we recorded other complications, i.e., meconium ileus, metabolic alkalosis and distal intestine obstructive syndrome (DIOS) as described [ 2 ].…”

Physical Activity Regulates TNFα and IL-6 Expression to Counteract Inflammation in Cystic Fibrosis Patients

“…The dysregulation of epithelial cells and innate immune function in the lungs results in increased, albeit ineffective, inflammation [ 8 ]. CF patients show progressive deterioration of lung function associated with the increased production of pro-inflammatory cytokines such as tumour necrosis factor α (TNFα), interleukin-6 (IL-6), and IL-8 in serum and in saliva [ 9 , 10 ]. In this scenario, physical activity (PA) plays a pivotal role in the treatment of chronic diseases characterised by increased inflammation status, including metabolic pathologies [ 11 ].…”