Adults’ Saliva Has More Anti-inflammatory Fatty Molecules
Adults with cystic fibrosis (CF) have significantly higher levels of anti-inflammatory oxylipins — a type of fatty molecule — and lower levels of pro-inflammatory fatty molecules in their saliva relative to healthy individuals, a study shows.
This suggests a shift toward an anti-inflammatory response in the fatty molecule profile in CF patients’ saliva that may reflect a compensatory mechanism for the chronic inflammation seen in these patients.
While the findings need to be confirmed in larger CF patient populations followed over time, they may help identify new biomarkers and therapeutic approaches for CF, the researchers noted.
The study, “Oxylipin profile in saliva from patients with cystic fibrosis reveals a balance between pro-resolving and pro-inflammatory molecules,” was published in the journal Scientific Reports.
Chronic inflammation is a hallmark of CF, affecting most tissues and organs. In the lungs, an increase in pro-inflammatory molecules and chronic infections “create a vicious circle of chronic airway inflammation,” the researchers wrote.
This causes destruction of lung tissue, ultimately limiting patients’ ability to breathe.
Previous studies showed that airway secretions from CF patients have higher levels of pro-inflammatory fatty molecules, such as oxylipins, relative to those with anti-inflammatory effects.
Oxylipins are signaling molecules derived from fatty acids, another type of fatty molecule, that regulate blood vessel and airway constriction, production of lung mucus and cytokines, and immune cell activity — all implicated in CF. Cytokines are molecules that mediate and regulate immune and inflammatory response.
As such, oxylipins may represent not only promising biomarkers to predict CF’s course and monitor treatment responses, but also targets of new therapeutic approaches.
Given that airway secretions are difficult to collect, particularly in pediatric patients, a team of researchers in Italy assessed whether the saliva of CF patients showed an altered fatty molecule profile relative to healthy people.
In previous work, the same team had shown that salivary cytokine levels were associated with lung disease severity in CF.
In the current study, the researchers analyzed levels of 65 oxylipins and four fatty acids in the saliva of 69 adults (37 men and 32 women) with CF, and 50 age- and sex-matched healthy individuals (used as controls).
Results showed that the salivary levels of 48 oxylipins and two fatty acids were significantly different between CF patients and controls, and that some of them were linked to pro-inflammatory cytokines levels in saliva.
A total of 15 of these fatty molecules contributed the most to accurately draw distinctions between the two groups.
Specifically, the salivary levels of four oxylipins — EpETE, DHET, 6ketoPGE1, and HDHA — with anti-inflammatory, airway widening, and immunosuppressive effects were significantly higher in CF patients relative to controls.
CF patients also showed significantly lower levels of nine oxylipins — 20-hydroxyPGF2A, PGB2, EpDPE, 9 K-12-ELA, bicyclo-PGE2, LTC4, 15oxoEDE, 20 hydroxyPGE2, and DHK-PGD2/PGE2 — mostly associated with pro-inflammatory and blood vessel and airway constriction effects.
The salivary levels of two fatty acids (oleic acid and linoleic acid) thought to be “strong modulators of inflammation” also were significantly reduced among CF patients, compared with controls, the researchers wrote.
Further analysis in CF patients’ saliva alone showed that higher levels of 19,20 DiHDPA were associated significantly with worse lung function, or moderate-to-severe lung disease. No other links between oxylipins and disease severity parameters were found.
These findings highlight that the pattern of oxylipins and fatty acids in CF patients’ saliva appears to incline toward “an anti-inflammatory response with an increase of molecules that reduce [blood vessel and airway constriction] which are the hallmark of CF chronic inflammation,” the team wrote.
This may represent “a long-standing ‘readaptation’ aimed to contrast chronic inflammation,” they added.
It remains uncertain whether this specific profile results from increased production of anti-inflammatory fatty molecules and reduced production of those with pro-inflammatory effects, or from the consumption of pro-inflammatory molecules.
More studies, following larger groups of patients over time, are needed to confirm these findings and better understand the role of fatty molecules in CF chronic inflammation.
Such findings may help identify prognostic and treatment response biomarkers in saliva — an easy, rapid, and poorly invasive approach — as well as develop “targeted therapies based on the modulation of oxylipins synthesis and degradation,” the team wrote.