Journal of Inflammation Research (Mar 2023)
Association Between Salivary Cytokines, Chemokines and Growth Factors and Salivary Gland Function in Children with Chronic Kidney Disease
Abstract
Julita Szulimowska,1 Anna Zalewska,1 Katarzyna Taranta-Janusz,2 Grażyna Marczuk-Kolada,3 Małgorzata Żendzian-Piotrowska,4 Mateusz Maciejczyk4 1Department of Restorative Dentistry, Medical University of Bialystok, Bialystok, Poland; 2Department of Pediatrics and Nephrology, Medical University of Bialystok, Bialystok, Poland; 3Department of Pedodontics, Medical University of Bialystok, Bialystok, Poland; 4Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, PolandCorrespondence: Mateusz Maciejczyk, Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, 2c Mickiewicza Street, Bialystok, 15-233, Poland, Email [email protected]: Chronic kidney disease (CKD) is a systemic inflammatory disease that leads to multiple organ complications not only in the kidneys and the cardiovascular system, but also in the oral cavity. CKD children experience reduced saliva secretion (hyposalivation), which leads to increased incidence of dental caries and significant impairment of patients’ quality of life. However, the causes of salivary gland dysfunction in children with CKD are unknown. The present study is the first to evaluate the inflammatory and anti-inflammatory profile in the saliva of children with CKD at different stages of renal failure with normal and reduced salivary gland function.Methods: Thirty children with CKD (age 9– 16) and thirty age- and gender-matched healthy children were classified for the study. Salivary inflammatory and anti-inflammatory profile were assayed using the multiplex ELISA assay.Results: We demonstrated statistically significant changes in salivary pro-inflammatory (↑TNF-α, ↓IL-7), anti-inflammatory (↑IL-10), Th1 (↑INF-γ, ↑IL-15), Th2 (↑IL-4, ↑IL-5, ↑IL-6, ↑IL-9) and Th17 (IL-17) cytokines as well as chemokines (↑MCP-1/CCL-2, ↑MIP-1α/CCL3, ↓MIP-1β/CCL4, ↓EOTAXIN/CCL11) and growth factors (↑G-CSF, ↑FGF) in unstimulated saliva of children with CKD compared to the controls. Although the evaluation of the salivary inflammatory profile does not indicate a particular dominance of any of the branches of the immune system, we observed a statistically significant increase in the concentration of all Th2 cytokines assayed. The multivariate regression analysis showed that the content of salivary cytokines, chemokines and growth factors depends on the secretory function of the salivary glands, ie, salivary flow, total protein concentration and amylase activity in the saliva. Salivary MIP-1α/CCL3 was the most effective to differentiate children with CKD and hyposalivation from patients with normal saliva secretion.Discussion: Inflammation is involved in salivary gland dysfunction in children with CKD, although further studies on in vitro and in vivo models are necessary to confirm this hypothesis.Keywords: chronic kidney disease, saliva, inflammation, salivary gland dysfunction, hyposalivation
