Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06558136
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-08-14
Brief Title:
Evaluation of Salivary Biomarker Levels in Individuals with Different Periodontal Conditions
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Evaluation of Salivary Interleukin-6 Interleukin-8 and LIGHT Protein Levels in Individuals with Different Periodontal Conditions
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In order to determine the pathogenesis of chronic inflammatory diseases the levels of various cytokines are examined in tissues and fluids taken from the body Recent publications have investigated the role of Interleukin-6 IL-6 Interleukin-8 IL-8 and LIGHT in chronic inflammatory diseases The aim of this study was to evaluate the levels of these cytokines in the saliva of healthy individuals with gingivitis and periodontitis and to investigate whether they are reliable biomarkers for the diagnosis of periodontitis
In our study all oral clinical parameters of 60 systemically healthy individuals 20 healthy 20 with gingivitis and 20 with periodontitis who were admitted to our clinic for routine periodontal control will be measured and saliva samples will be taken from the patients IL-6 IL-8 and LIGHT biomarkers emphasizing inflammation in saliva samples will be determined by enzyme-linked immunoassay ELISA Then statistical analyses will be performed to interpret the difference in cytokine levels between the groups and the relationship between these cytokines and clinical parameters
Possible significant differences between cytokine levels will reveal that these proteins and enzymes can be utilized as a diagnostic tool in periodontal diseases to distinguish periodontal disease status from healthy or as a guide for treatments
In our study all oral clinical parameters of 60 systemically healthy individuals 20 healthy 20 with gingivitis and 20 with periodontitis who were admitted to our clinic for routine periodontal control will be measured and saliva samples will be taken from the patients IL-6 IL-8 and LIGHT biomarkers emphasizing inflammation in saliva samples will be determined by enzyme-linked immunoassay ELISA Then statistical analyses will be performed to interpret the difference in cytokine levels between the groups and the relationship between these cytokines and clinical parameters
Possible significant differences between cytokine levels will reveal that these proteins and enzymes can be utilized as a diagnostic tool in periodontal diseases to distinguish periodontal disease status from healthy or as a guide for treatments
Detailed Description:
The aim of this clinical study is to comparatively examine the levels of IL-6 IL-8 and LIGHT Protein in saliva samples obtained from periodontally healthy individuals with gingivitis and periodontitis who presented to our clinic for routine periodontal controls In line with the results obtained it is planned to determine the potential of these biochemical mediators to be used as a diagnostic marker in the diagnosis of periodontal disease
Periodontitis is a multifactorial disease involving 10-15 of the world39s adult population developing due to microbial dental plaque and characterized by loss of clinical attachment and destruction of connective tissue and alveolar bone If left untreated it causes inflammation to penetrate into deeper tissues and alter bone homeostasis leading to tooth loss
Gingivitis is an inflammation of the gingiva that does not cause destruction in the surrounding tissues surrounding the tooth and is characterized by edema in the gums and bleeding in more than 10 of all areas in the mouth According to the 2017 Classification of Periodontal Diseases gingivitis is divided into two as dental plaque-related gingivitis and non-dental plaque-related gingivitis Gingivitis is often painless and rarely spontaneous bleeding is observed and for these reasons individuals may recognize the disease late Therefore early diagnosis of gingivitis is important to prevent the transformation of gingivitis into periodontitis characterized by progressive bone destruction and connective tissue destruction
Studies have shown that there are more than 700 bacteria with the ability to colonize in the human oral cavity but an average of 200 to 300 bacterial species in an individual39s mouth Among these bacteria there are bacteria associated with gingival health such as Porphyromonas gingivalis Pg Tannerella forsythensis Tf and Treponema denticola Td which are called red complex bacteria Fusobacterium nucleatum Fn subspecies Prevotella intermedia Pi and Aggregatibacter actinomycetemcomitans Aa which do not belong to any group have been associated with active tissue destruction and periodontitis disease progression
According to the key plaque hypothesis which is one of the currently accepted plaque hypotheses the ability of highly pathogenic bacteria especially P Gingivalis and Aggregatibacter Actinomycetemcomitans to generate host immune response and cause tissue destruction despite their low amount in plaque concentration has been emphasized It has been shown that pathogenic bacteria affect the host immune response rather than direct inflammatory bone and connective tissue destruction One of the important points in the pathogenesis of periodontal disease is cytokines a member of the acquired immune system Studies have shown that the amount of proinflammatory cytokines such as interleukin-6 IL-6 IL-8 interleukin-1 IL-1 tumor necrosis factor- α TNF-α increase in blood plasma saliva and gingival groove fluid
LIGHT protein TNFSF-14 a member of the tumor necrosis factor superfamily TNFSF is mostly secreted by T cells and immature dendritic cells but it is also secreted by cells with immunological roles such as monocytes granulocytes splenocytes and spleen cells LIGHT can bind HVEM and three membrane-bound TNFSF signaling receptors namely lymphotoxin beta receptor LTβR and DcR3 LIGHT-LTβR binding has been shown to induce apoptosis While HVEM is expressed on endothelial dendritic natural killer T and B cells LTβR is expressed on fibroblasts monocytes endothelial epithelial and stromal cells The interaction of LIGHT protein with HVEM or LTβR results in Nuclear-Factor-kappaB activation and ultimately cytokine production It has also been shown that LIGHT protein can costimulate the T cellular response via HVEM including CD4 and CD8 T cells
Rheumatoid arthritis is a chronic destructive inflammatory disease Proinflammatory cytokines such as IL-1 TNF-a matrix metalloproteinase MMP-8 MMP-9 are increased in rheumatoid arthritis as well as in periodontitis For these reasons there are similarities between the immunopathogenesis of periodontitis and rheumatoid arthritis In a study conducted in rheumatoid arthritis patients LIGHT protein was shown to be an important proinflammatory biomarker positively correlated with bone destruction and statistically increased bone destruction In another study conducted in patients with rheumatoid arthritis serum levels of LIGHT protein were evaluated and it was shown that increased levels of LIGHT increased RANKL-dependent osteoclastogenesis and increased osteoclast formation independently of RANKL Another conclusion from this study is that LIGHT protein may play a role in immunopathogenic conditions associated with local and systemic bone loss
In another study conducted in rheumatoid arthritis patients LIGHT increased the inflammatory response in synovial fibroblast cells and was suggested to be a new anti-cytokine therapy target for the treatment of rheumatoid arthritis
In a study conducted in patients with multiple myeloma bone disease LIGHT was shown to increase osteoclastogenesis inhibit osteoblastic proteins osteocalcin bone sialoprotein and osterix formation and inhibit sclerostin osteoblastogenesis from monocytes
In a study by Fan et al it was investigated whether LIGHT protein is a potential inflammatory biomarker In 566 patients LIGHT protein was shown to increase 16-fold in blood serum in the presence of pneumonia an inflammatory disease
Type 2 diabetes mellitus is characterized by dysregulation of carbohydrate lipid and protein metabolism and is caused by impaired insulin secretion from pancreatic islet cells insulin resistance or a combination of both Studies have shown periodontitis as the 6th complication of diabetes mellitus and a positive two-way correlation has been proven In a study conducted in patients with type 2 diabetes mellitus it was shown that LIGHT protein showed dysfunction in pancreatic islet cells increased inflammatory cytokine secretion and increased inflammatory response formation in endothelial cells
In a study conducted in patients with multiple myeloma bone disease LIGHT was shown to increase osteoclastogenesis inhibit the formation of osteoblastic proteins osteocalcin bone sialoprotein and osterix and inhibit sclerostin osteoblastogenesis from monocytes investigated whether LIGHT protein is a potential inflammatory biomarker In 566 patients it was shown that LIGHT protein increased 16-fold in blood serum in the presence of pneumonia an inflammatory disease
Type 2 diabetes mellitus is characterized by dysregulation of carbohydrate lipid and protein metabolism and is caused by impaired insulin secretion from pancreatic islet cells insulin resistance or a combination of both Studies have shown that periodontitis is the 6th complication of diabetes mellitus and a positive two-way correlation has been proven In a study conducted in patients with type 2 diabetes mellitus LIGHT protein was shown to show dysfunction in pancreatic islet cells increased secretion of inflammatory cytokines and increased inflammatory response in endothelial cells
The starting point of our study was a study published in 2024 that examined proinflammatory cytokines in the gingival groove fluid after periodontal surgery and aimed to find a potential new biomarker According to this study LIGHT was shown to stimulate the formation of proinflammatory cytokines IL-6 and IL-8 and MMP-9 in human gingival fibroblasts and to be associated with increased periodontal pocket probing depth formation at 12 months after surgery It has been suggested that LIGHT protein causes tissue destruction in human gingival fibroblast cells causes tissue loss in soft tissue and bone and contributes to the development of periodontitis In this study it was emphasized that more studies are needed to evaluate the relationship between LIGHT and periodontitis
Interleukin-6 is a multifunctional cytokine defined as a B-cell differentiation factor involved in the maturation of antibody-producing cells IL-6 is a single-chain protein produced by T cells B cells monocytes fibroblasts and some other cell types IL-6 can transmit signals to cells in two ways conventional receptor-dependent signaling and trans signaling associated with the soluble IL-6 receptor One of the most important systemic effects of IL-6 is the induction of an acute phase response This acute phase response is the induction of proinflammatory cytokine production and stimulation of neutrophil chemotaxis It also increases C-reactive protein CRP levels the most common acute phase protein in humans It also has properties such as increasing T cell activation and differentiation and increasing macrophage differentiation
IL-6 also increases endothelial cell proliferation leading to IL-8 and monocyte chemoattractant protein secretion As a result of these processes it causes leukocytes to come to the site of inflammation It also increases the secretion of proinflammatory MMP enzymes together with Interleukin-1
In a study the effect of non-surgical initial treatment on IL-6 levels in healthy and periodontitis patients was examined According to the results of this study baseline gingival groove fluid IL-6 levels were found to be significantly higher in periodontitis patients than in healthy patients After non-surgical periodontal treatment a statistically significant decrease in IL-6 levels was observed This study suggests that IL-6 may be a biomarker that can be used in the diagnosis of periodontitis
In a study conducted in rats it was shown that inhibition of IL-6 secretion in the setting of experimental periodontitis halted the proinflammatory activity induced by IL-6 and reduced alveolar bone resorption and decreased RANKL production
In a cross-sectional study IL-6 and IL-8 levels in saliva and gingival groove fluid obtained from healthy individuals and individuals with periodontitis were analyzed In the results IL-6 and IL-8 levels were found to be higher in both saliva and gingival groove fluid in patients with periodontitis than in healthy patients
IL-8 is a proinflammatory chemokine and its expression is primarily regulated by activator protein and nuclear factor-kappa β-mediated transcriptional activity IL-8 expression has been shown to be regulated by stimuli such as TNF-α IL-1β steroid hormones including inflammatory signals IL-8 has been characterized on the basis of its chemotactic activity and its ability to cause degranulation of human neutrophils In vitro it has two main effects chemotaxis and release of granule enzymes It acts as a chemoattractant and neutrophil activator for cytokines at inflammatory sites and can be secreted by endothelial cells gingival fibroblasts monocytes neutrophils and phagocytes The secretion of IL-8 facilitates the migration of neutrophils from highly vascularized gingival tissue to the gingival groove IL-8 is the earliest secreted proinflammatory cytokine from gingival epithelial cells stimulated by pathogenic bacteria such as P Gingivalis and T Forsythia and can persist for as long as one week after secretion
In a literature review study it was emphasized that the number of IL-8 levels increased significantly in the presence of periodontitis but more studies are needed due to different results in various studies In another literature review study it was emphasized that IL-8 serum level may be a potential biomarker in the evaluation of periodontitis but more studies are needed
According to the above information there is no study in the literature evaluating IL-6 IL-8 and LIGHT levels in saliva samples in terms of periodontal disease Our study aimed to investigate the changes of these cytokines in the presence of periodontal disease by comparatively examining IL-6 IL-8 and LIGHT levels in saliva samples obtained from healthy individuals with gingivitis and periodontitis to show their potential to be used in the diagnosis of disease or to provide preliminary information for future treatments that may be performed through these cytokine pathways
Periodontitis is a multifactorial disease involving 10-15 of the world39s adult population developing due to microbial dental plaque and characterized by loss of clinical attachment and destruction of connective tissue and alveolar bone If left untreated it causes inflammation to penetrate into deeper tissues and alter bone homeostasis leading to tooth loss
Gingivitis is an inflammation of the gingiva that does not cause destruction in the surrounding tissues surrounding the tooth and is characterized by edema in the gums and bleeding in more than 10 of all areas in the mouth According to the 2017 Classification of Periodontal Diseases gingivitis is divided into two as dental plaque-related gingivitis and non-dental plaque-related gingivitis Gingivitis is often painless and rarely spontaneous bleeding is observed and for these reasons individuals may recognize the disease late Therefore early diagnosis of gingivitis is important to prevent the transformation of gingivitis into periodontitis characterized by progressive bone destruction and connective tissue destruction
Studies have shown that there are more than 700 bacteria with the ability to colonize in the human oral cavity but an average of 200 to 300 bacterial species in an individual39s mouth Among these bacteria there are bacteria associated with gingival health such as Porphyromonas gingivalis Pg Tannerella forsythensis Tf and Treponema denticola Td which are called red complex bacteria Fusobacterium nucleatum Fn subspecies Prevotella intermedia Pi and Aggregatibacter actinomycetemcomitans Aa which do not belong to any group have been associated with active tissue destruction and periodontitis disease progression
According to the key plaque hypothesis which is one of the currently accepted plaque hypotheses the ability of highly pathogenic bacteria especially P Gingivalis and Aggregatibacter Actinomycetemcomitans to generate host immune response and cause tissue destruction despite their low amount in plaque concentration has been emphasized It has been shown that pathogenic bacteria affect the host immune response rather than direct inflammatory bone and connective tissue destruction One of the important points in the pathogenesis of periodontal disease is cytokines a member of the acquired immune system Studies have shown that the amount of proinflammatory cytokines such as interleukin-6 IL-6 IL-8 interleukin-1 IL-1 tumor necrosis factor- α TNF-α increase in blood plasma saliva and gingival groove fluid
LIGHT protein TNFSF-14 a member of the tumor necrosis factor superfamily TNFSF is mostly secreted by T cells and immature dendritic cells but it is also secreted by cells with immunological roles such as monocytes granulocytes splenocytes and spleen cells LIGHT can bind HVEM and three membrane-bound TNFSF signaling receptors namely lymphotoxin beta receptor LTβR and DcR3 LIGHT-LTβR binding has been shown to induce apoptosis While HVEM is expressed on endothelial dendritic natural killer T and B cells LTβR is expressed on fibroblasts monocytes endothelial epithelial and stromal cells The interaction of LIGHT protein with HVEM or LTβR results in Nuclear-Factor-kappaB activation and ultimately cytokine production It has also been shown that LIGHT protein can costimulate the T cellular response via HVEM including CD4 and CD8 T cells
Rheumatoid arthritis is a chronic destructive inflammatory disease Proinflammatory cytokines such as IL-1 TNF-a matrix metalloproteinase MMP-8 MMP-9 are increased in rheumatoid arthritis as well as in periodontitis For these reasons there are similarities between the immunopathogenesis of periodontitis and rheumatoid arthritis In a study conducted in rheumatoid arthritis patients LIGHT protein was shown to be an important proinflammatory biomarker positively correlated with bone destruction and statistically increased bone destruction In another study conducted in patients with rheumatoid arthritis serum levels of LIGHT protein were evaluated and it was shown that increased levels of LIGHT increased RANKL-dependent osteoclastogenesis and increased osteoclast formation independently of RANKL Another conclusion from this study is that LIGHT protein may play a role in immunopathogenic conditions associated with local and systemic bone loss
In another study conducted in rheumatoid arthritis patients LIGHT increased the inflammatory response in synovial fibroblast cells and was suggested to be a new anti-cytokine therapy target for the treatment of rheumatoid arthritis
In a study conducted in patients with multiple myeloma bone disease LIGHT was shown to increase osteoclastogenesis inhibit osteoblastic proteins osteocalcin bone sialoprotein and osterix formation and inhibit sclerostin osteoblastogenesis from monocytes
In a study by Fan et al it was investigated whether LIGHT protein is a potential inflammatory biomarker In 566 patients LIGHT protein was shown to increase 16-fold in blood serum in the presence of pneumonia an inflammatory disease
Type 2 diabetes mellitus is characterized by dysregulation of carbohydrate lipid and protein metabolism and is caused by impaired insulin secretion from pancreatic islet cells insulin resistance or a combination of both Studies have shown periodontitis as the 6th complication of diabetes mellitus and a positive two-way correlation has been proven In a study conducted in patients with type 2 diabetes mellitus it was shown that LIGHT protein showed dysfunction in pancreatic islet cells increased inflammatory cytokine secretion and increased inflammatory response formation in endothelial cells
In a study conducted in patients with multiple myeloma bone disease LIGHT was shown to increase osteoclastogenesis inhibit the formation of osteoblastic proteins osteocalcin bone sialoprotein and osterix and inhibit sclerostin osteoblastogenesis from monocytes investigated whether LIGHT protein is a potential inflammatory biomarker In 566 patients it was shown that LIGHT protein increased 16-fold in blood serum in the presence of pneumonia an inflammatory disease
Type 2 diabetes mellitus is characterized by dysregulation of carbohydrate lipid and protein metabolism and is caused by impaired insulin secretion from pancreatic islet cells insulin resistance or a combination of both Studies have shown that periodontitis is the 6th complication of diabetes mellitus and a positive two-way correlation has been proven In a study conducted in patients with type 2 diabetes mellitus LIGHT protein was shown to show dysfunction in pancreatic islet cells increased secretion of inflammatory cytokines and increased inflammatory response in endothelial cells
The starting point of our study was a study published in 2024 that examined proinflammatory cytokines in the gingival groove fluid after periodontal surgery and aimed to find a potential new biomarker According to this study LIGHT was shown to stimulate the formation of proinflammatory cytokines IL-6 and IL-8 and MMP-9 in human gingival fibroblasts and to be associated with increased periodontal pocket probing depth formation at 12 months after surgery It has been suggested that LIGHT protein causes tissue destruction in human gingival fibroblast cells causes tissue loss in soft tissue and bone and contributes to the development of periodontitis In this study it was emphasized that more studies are needed to evaluate the relationship between LIGHT and periodontitis
Interleukin-6 is a multifunctional cytokine defined as a B-cell differentiation factor involved in the maturation of antibody-producing cells IL-6 is a single-chain protein produced by T cells B cells monocytes fibroblasts and some other cell types IL-6 can transmit signals to cells in two ways conventional receptor-dependent signaling and trans signaling associated with the soluble IL-6 receptor One of the most important systemic effects of IL-6 is the induction of an acute phase response This acute phase response is the induction of proinflammatory cytokine production and stimulation of neutrophil chemotaxis It also increases C-reactive protein CRP levels the most common acute phase protein in humans It also has properties such as increasing T cell activation and differentiation and increasing macrophage differentiation
IL-6 also increases endothelial cell proliferation leading to IL-8 and monocyte chemoattractant protein secretion As a result of these processes it causes leukocytes to come to the site of inflammation It also increases the secretion of proinflammatory MMP enzymes together with Interleukin-1
In a study the effect of non-surgical initial treatment on IL-6 levels in healthy and periodontitis patients was examined According to the results of this study baseline gingival groove fluid IL-6 levels were found to be significantly higher in periodontitis patients than in healthy patients After non-surgical periodontal treatment a statistically significant decrease in IL-6 levels was observed This study suggests that IL-6 may be a biomarker that can be used in the diagnosis of periodontitis
In a study conducted in rats it was shown that inhibition of IL-6 secretion in the setting of experimental periodontitis halted the proinflammatory activity induced by IL-6 and reduced alveolar bone resorption and decreased RANKL production
In a cross-sectional study IL-6 and IL-8 levels in saliva and gingival groove fluid obtained from healthy individuals and individuals with periodontitis were analyzed In the results IL-6 and IL-8 levels were found to be higher in both saliva and gingival groove fluid in patients with periodontitis than in healthy patients
IL-8 is a proinflammatory chemokine and its expression is primarily regulated by activator protein and nuclear factor-kappa β-mediated transcriptional activity IL-8 expression has been shown to be regulated by stimuli such as TNF-α IL-1β steroid hormones including inflammatory signals IL-8 has been characterized on the basis of its chemotactic activity and its ability to cause degranulation of human neutrophils In vitro it has two main effects chemotaxis and release of granule enzymes It acts as a chemoattractant and neutrophil activator for cytokines at inflammatory sites and can be secreted by endothelial cells gingival fibroblasts monocytes neutrophils and phagocytes The secretion of IL-8 facilitates the migration of neutrophils from highly vascularized gingival tissue to the gingival groove IL-8 is the earliest secreted proinflammatory cytokine from gingival epithelial cells stimulated by pathogenic bacteria such as P Gingivalis and T Forsythia and can persist for as long as one week after secretion
In a literature review study it was emphasized that the number of IL-8 levels increased significantly in the presence of periodontitis but more studies are needed due to different results in various studies In another literature review study it was emphasized that IL-8 serum level may be a potential biomarker in the evaluation of periodontitis but more studies are needed
According to the above information there is no study in the literature evaluating IL-6 IL-8 and LIGHT levels in saliva samples in terms of periodontal disease Our study aimed to investigate the changes of these cytokines in the presence of periodontal disease by comparatively examining IL-6 IL-8 and LIGHT levels in saliva samples obtained from healthy individuals with gingivitis and periodontitis to show their potential to be used in the diagnosis of disease or to provide preliminary information for future treatments that may be performed through these cytokine pathways
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None