The feasibility of monitoring NF‐κB associated cytokines: TNF‐α, IL‐1α, IL‐6, and IL‐8 in whole saliva for the malignant transformation of oral lichen planus

Abstract

Previous investigations have demonstrated that immune activation and chronic inflammation may be one of the causes of oncogenesis. A previous study from our lab has shown significant increases of NF-kappaB dependent cytokines, TNF-alpha, IL-1alpha, IL-6, and IL-8 in different oral fluids from oral lichen planus (OLP) patients. The aim of this analysis was to explore the potential of detecting these cytokines in whole unstimulated saliva (WUS) in monitoring the malignant transformation of OLP. Thirteen patients with OLP (with epithelial dysplasia), 13 cases with oral squamous cell carcinoma (OSCC), and 13 age-sex matched controls were enrolled in the study. The WUS samples were collected and the level of TNF-alpha, IL-1alpha, IL-6, and IL-8 in WUS was determined by ELISA. In moderate and severe dysplasia, the level of each cytokine was significantly higher than in control. In moderate dysplasia, TNF-alpha and IL-1alpha were significantly increased at a level without difference from OSCC, but IL-6 and IL-8 was detected at a concentration significantly lower than OSCC. In severe dysplasia, the level of TNF-alpha was also not significantly different from that of OSCC, and the level of IL-1alpha, IL-6, and IL-8 was still significantly lower than that of OSCC. The level of four cytokines between smokers and non-smokers in each group did not show a significant difference. These results indicate that the change of NF-kappaB dependent cytokines in WUS may in part reflect the malignant transformation of OLP and the analysis of these cytokines and may provide a useful, non-invasive surrogate endpoint for monitoring malignant transformation as well as the therapeutic response of OLP. This is the first in vivo study utilizing saliva to confirm preclinical data that NF-kappaB is upregulated in oral carcinogenesis.

Current Status of Salivary Hormone Analysis

“…An active, energy-dependant mode of transport causes difficulties in interpreting the salivary concentrations, because concentrations of salivary peptides do not always correlate as well with plasma concentrations as do concentrations of passively diffused steroids. For certain cytokines, such as tumor necrosis factor and leptin, lower concentrations appear in saliva than in plasma (10,11 ). For other cytokines, such as epidermal growth factor (12 ) and ghrelin (13 ), saliva concentrations have been observed to be equal to or higher than those in plasma.…”

Proteomics Analysis of Cells in Whole Saliva from Oral Cancer Patients via Value-added Three-dimensional Peptide Fractionation and Tandem Mass Spectrometry

“…A natural producer of glutamic acid E. corrodens (2) Anaerobic bacterium normally in the adult human oral cavity but that may become an opportunistic pathogen, especially in immunocompromised individuals Escherichia coli (5) One of the foremost causes of food poisoning, also found in the human digestive tract Haemophilus influenzae (13) An opportunistic pathogen involved in numerous diseases Lactococcus lactis subsp. lactis (11) Used in the dairy industry for cheese, yogurt, and buttermilk production Leifsonia xyli subsp.…”

“…Cannot tolerate oxygen and is one of the methane-producing microbes Mycobacterium leprae (2) The bacterium that causes leprosy Mycobacterium tuberculosis (2) The major cause of tuberculosis Mycoplasma genitalium (2) Causes reproductive tract infections P. multocida (5) A pathogenic bacteria causing many serious diseases in humans and animals Porphyromonas gingivalis (8) One of the leading causes of periodontal disease…”

“…Causes food-borne gastroenteritis Streptococcus mutans (5) A dental pathogen, is the leading cause of tooth decay worldwide Streptococcus pneumoniae (21) Causes pneumonia, blood infections, and meningitis…”

Association between the clinical severity of oral lichen planus and anti-TPO level in thyroid patients

“…5 Elevated levels of IL-8 in the serum of OLP patients have been recorded and reported in several studies. 6,7,8,9 It has also been reported that the clinical severity of OLP is directly associated with the IL-8 level in the serum. 9 Declaration of Interests: The authors certify that they have no commercial or associative interest that represents a conflict of interest in connection with the manuscript.…”