Expression of periodontal interleukin‐6 protein is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases

It has been well documented that interleukin (IL)-6 plays an essential role in periodontal disease (1). Our recent study on periodontal expression of genes known to be involved in periodontal disease showed a trend of increase in IL-6 mRNA expression in periodontal tissue across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone, and patients with both diseases (p=0.02) (2). No trend of increase across the three groups was found for IL-1β, TNFα, and MMP-8, while a marginal trend of increase was observed for MMP-1 (p=0.05). Given that periodontal disease in diabetic patients is more severe than that in nondiabetic patients, these findings suggest that IL-6 may contribute to the progression of periodontal disease. Besides this report, previous studies have also provided evidence supporting that IL-6 is an important cytokine involved in the pathogenesis of periodontal disease. Interleukin-6 is abundant in the inflammatory lesions in periodontal tissues and activates fibroblasts in the presence of soluble IL-6 receptor (3). Interleukin-6 is a potent stimulator for MMP production (1). In addition to periodontal disease, it has been well established that IL-6, along with other pro-inflammatory cytokines (such as TNF-aand IL-1b), is involved in the production of the chronic and low-grade inflammation that contributes to other diabetic complications such as cardiovascular diseases (4–6). It has been proposed that IL-6 released from diseased periodontal tissue enters the blood circulation and stimulates both immune and nonimmune-related cells by activating the Janus kinase (JAK)/signal transducers and activator of transcription (STAT) and the Src homology 2-containing tyrosine phosphatase (SHP-2)/ERK/MAPK pathways and upregulating gene expression involved in inflammation (5). Although we have demonstrated a trend of increase in periodontal IL-6 expression at the mRNA level across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases (2), the periodontal expression of IL-6 at the protein level in these patients has not been investigated. While an increase in mRNA expression level of a gene is frequently associated with an increase in its protein level, the extent of protein expression can be different from that of mRNA expression due to the translational regulation by the same stimulus. For example, we showed previously that the stimulation of CD14 expression at the mRNA and protein levels in U937 histiocytes by lipopolysaccharide (LPS) and high glucose was 15-fold and 45-fold as compared to those by LPS and normal glucose, respectively (7). Thus, it is important to determine the IL-6 protein level in periodontal tissue to fully elucidate the impact of periodontal disease and diabetes on IL-6 expression. In this study, we recruited 35 patients with or without periodontal disease and diabetes and collected periodontal tissue specimens at the time of necessary surgical intervention and analyzed periodontal IL-6 protein expression levels using immunohistochemistry. Quantitative data showed that periodontal IL-6 expression at the protein level is significantly increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone, and patients with both diseases.