Salivary IL-1 Alpha and IL-1 Beta Levels Are Associated with Oral Mucosal Activity in Behcet’s Disease

Abstract

Background/Purpose:Recurrent oral aphthous ulcers are the common manifestation of the Behçet’s disease (BD), and they are indistinguishable from ulcers of recurrent aphthous stomatitis (RAS). There is no reliable biomarker reflecting disease activity in BD, and systemic acute phase reactants are not helpful in evaluation of active disease, especially in patients with predominantly mucocutaneous activity. We aimed to assess the potential of salivary interleukin-1 alpha and beta (IL-1α and IL-1β) concentrations as well as two S100 proteins, namely S100A12 (calprotectin) and S100A13 in comparison to their serum levels in BD, RAS, and healthy controls.Methods:A total of 67 patients with BD, 43 patients with RAS, and 22 healthy controls with no history of aphthous ulcers or other oral mucosal disorders (NA) comprised the study group. BD patients fulfilled the ISG criteria for the diagnosis, and patients with active systemic disease were excluded. Patients with BD and RAS were classified as active and inactive according to the presence or absence of aphthous ulcers at the time of sample collection. Unstimulated saliva and serum samples were collected after overnight fasting. IL-1α, IL-1β, S100A13 and calprotectin levels were measured by ELISA, and concomitant measurements of ESR and serum CRP levels of BD patients were recorded.Results:At the time of sample collection, 38 BD patients (18 male, mean age: 39,1±10,3) were classified as active and 29 patients (18 male, mean age: 38,9±10,5) as inactive. Similarly, 19 patients with RAS (11 male, mean age: 36,6±8,7) were active and 24 patients (7 male, mean age: 36,7±10,1) were inactive state. Mean values of salivary and serum ELISA measurements are given in Table 1. Salivary IL-1α and IL-1β,levels were higher in BD patients compared to RAS and NA even during inactive state (IL-1α p<0.001 for RAS and p<0.001 for NA, IL-1β p<0.001 for RAS and p=0.003 for NA). There was a correlation between IL-1α and IL-1βlevels, but IL-1α increase was more prominent in active BD patients. No correlation was detected between salivary IL-1α and S100A13 levels. Serum CRP and ESR were within normal range in BD patients, and they showed no correlation with salivary measurements. SALIVA SERUMIL-1α(pg/ml)IL-1β(pg/ml)S100A12(ng/ml)S100A13(ng/ml)IL-1α(pg/ml)IL-1β(pg/ml)S100A12(ng/ml)S100A13(ng/ml)BD active (n=38)21475.149.11.813.917.857.70.6BD inactive (n=29)14924.748.41.512.418.367.10.9RAS active (n=19)13242.360.11.835.222.8110.01.9RAS inactive (n=24)2820.737.01.928.523.2146.01.7Healthy controls (n=22)3611.830.31.331.423.3188.01.2Conclusion:These results suggest a role for IL-1α and IL-1βin the development of oral aphthous ulcers. S100A13 is known to be involved in controlled secretion of IL-1α. Increased IL-1a levels without an increase in S100A13 levels may suggest that pyroptosis or other causes of cellular damage is the main source of salivary IL-1α. Further studies are necessary both to improve saliva collection and analysis methods and to search the biomarker potential of salivaryIL-1α and IL-1βconcentrations in the management of mucocutaneous and systemic manifestations of BD.