Inflammation of the gums and supporting tissues of teeth, known as chronic periodontitis, can be caused by one or many microbes. The alveolar bone and periodontal ligament gradually deteriorate, leading to pockets, recession, or both. A form of gum disease known as aggressive periodontitis can strike healthy people. The quantity of alveolar bone surrounding numerous permanent teeth decreases rapidly and significantly in this situation. The amount of local irritants present does not match the magnitude of the harm that has been diagnosed.

Both scenarios require periodontopathogens as the disease initiator. But it takes more than that for the disease to develop and spread. The interplay between the human immune system and periodontal microbes influences the onset, progression, and severity of periodontal disease. Cytokines, prostaglandins, and acute phase proteins are produced by the host in reaction to endotoxins and mediators of tissue rupture released by bacteria. Fibrinogen and C reactive protein are two of numerous acute-phase proteins released by the natural host in response to infections, ischemia necrosis, or wounds. Periodontal disease patients have an increased level of specific acute-phase proteins in their plasma, serum, or gingival crevicular fluid (GCF) [1-3].

Soluble proteins known as cytokines are pivotal in initiating and propagating immune and inflammatory responses. Among the many important functions performed by the multi-functional cytokine interleukin-6 (IL-6) during the acute-phase response is the regulation of protein synthesis. As a marker of inflammation in periodontal disease, it has been the subject of substantial research. In reaction to an infection or injured lesion, IL-6 is rapidly produced and sends a crucial signal all over the body. In response to IL-6, hepatocytes display an upregulation of many acute-phase proteins, such as C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, hepcidin, haptoglobin, and antichymotrypsin. The levels of albumin, fibronectin, transferrin, and cytochrome p450, on the other hand, drop dramatically.

Inflammatory mediators and pro-inflammatory cytokines, such as C-reactive protein and interleukin-6, are associated with periodontal disease indicators. Bacterial lipopolysaccharides and interleukin-6 promote hepcidin synthesis, an acute-phase protein that blocks duodenal iron absorption. Hepcidin is a very cysteine-rich, positively charged peptide. The liver and kidneys produce this molecule primarily for the purpose of regulating iron metabolism. Hepatocytes, macrophages, duodenal enterocytes, and the majority of cells' plasma membranes have the iron exporter ferroportin-I, with which serum hepcidin interacts particularly [4-6].  Reduced transferrin saturation causes diminished erythropoiesis, which in turn causes anaemia in chronic illness. This is caused by the increased levels of hepcidin in the bloodstream, which are initiated by inflammatory factors such as chronic periodontitis. Once ferroportin is released from the cell surface, it is taken inside and eventually broken down.

Inflammatory disorders that persist over an extended period of time, such cancer, autoimmune diseases, or recurrent infections, can lead to a decrease in the production of red blood cells, a condition known as chronic sickness anaemia. New studies show that anaemia can develop in situations where there is rapid and severe inflammation, such in serious diseases, or in situations where there is less inflammation but it lasts longer, like in obesity, old age, and kidney disease. Many considerations point to "anaemia of inflammation" (AI) as a better description than "anaemia of chronic disease." Hepcidin and interleukin-6 serum levels were found to be increased in patients with chronic periodontitis, according to a 2015 study by Carvalho. These levels were lower in healthy persons. All the way from six to eight, inclusive, are the possible values.

At this time, studies examining hepcidin concentrations in patients with advanced periodontitis are scarce. Patients with aggressive periodontitis and those with chronic periodontitis will have their serum hepcidin levels compared in this study. Patients with aggressive or chronic periodontitis will have their interleukin-6 and hepcidin levels measured both before and after the first phase of periodontal treatment [8,9].

Participants were chosen at random from the periodontology division's outpatient Department of Dentistry, Government Medical College and Hospital, Siddipet, between April 2024 to March 2025. A case-control approach was used in the study. Participants were recruited with a glance towards the future. Thirty persons were selected for the investigation. The periodontal health of ten people in Group I was excellent. (The study group, which is part of the control group) There are 10 people in Group II who have a chronic periodontitis diagnosis. For this study, we will be using ten patients with severe periodontitis as part of Group III [10].

Inclusion criteria -

• Between the ages of 15 and 55.
• Open to all genders.
• A minimum of 20 teeth must be present.
• The control group consists of individuals in group I who have satisfactory periodontal health. The study group comprises the following patients:

1. a) Group II: patients diagnosed with chronic periodontitis and exhibiting clinical attachment loss of at least 5 mm, affecting over thirty percent of the patient's teeth.

Group III patients exhibit severe periodontitis and experience attachment loss in a minimum of three permanent teeth, excluding the incisors and first molars.

Exclusion criteria

• Individuals who engage in the act of smoking.
• Both acute and chronic infections.
• Individuals suffering from systemic illnesses, autoimmune disorders, and those who have had organ transplantation
• Medically compromised individuals encompass those with weakened immune systems, unregulated diabetes, high blood pressure, cancer, stroke, bleeding disorders, and significant bone loss (osteoporosis).
• Individuals consuming iron supplements for the purpose of treating anaemia.
• A patient who received periodontal therapy in the past six months.
• The physiological processes of producing milk and becoming pregnant. •Prior utilisation of NSAIDs (non-steroidal anti-inflammatory medications) and antibiotics within the three-month period preceding the study.
• Individuals who consume bisphosphonates.

Table 1. DESCRIPTIVE STATISTICS

Table 2: In Group III, a paired t test was used to compare the mean values before and after treatment.

Table 3: Group I, Group II, and Group III parameter mean baseline values were compared using an ANOVA.

*There is statistically significant (p<0.05) variation in the mean baseline values of all the variables between groups 1, 2, and 3.

Table 4: Comparing the average three-month values of Group II and Group III parameters using independent T tests

In response to a microbial harm, the bones and soft tissues that support teeth deteriorate in periodontal disease, a chronic inflammatory disorder with multiple underlying causes. The presence of microorganisms is essential for periodontitis's underlying causes, but it is insufficient for the disease to progress or worsen on

its own. The interaction between periodontal microorganisms and the human immune system influences the onset, progression, and severity of periodontal disease. In reaction to endotoxin production by bacteria, the host cell synthesises acute phase proteins that cause tissue breakdown.

The localised infections caused by periodontitis can significantly affect the general health of animals and people, according to scientific study. Periodontitis patients have been found to have elevated IL-6 levels [11,12]. Hepcidin, an acute phase protein, can be produced by the liver in response to an elevation in IL-6. Hepcidin, which was found in 2001 by Park et al., is believed to play a role in the onset of inflammatory anaemia. Anaemia and periodontal disease are clearly linked, according to multiple study. In theory, anaemia could occur in people with periodontitis due to higher levels of IL-6 and Hepcidin.

An increase in oxidative stress has been associated with anaemia. An imbalance favouring oxidation results from low iron levels, which cause hypoxia in the tissues and reduced synthesis of iron-containing antioxidant proteins. When blood oxygen levels drop, the periodontium may react differently to local irritation, which can lead to periodontal injury. This condition is known as anaemia. Anaemia and periodontal disease are both linked, according to the research [13,14].

Finding a link between IL-6, hepcidin, and periodontal disease levels in the blood is the primary goal of our research. Phase 1 periodontal therapy's ability to reduce IL-6 and hepcidin concentrations is what we're aiming to evaluate. Participants in the current study were divided into three groups: those with no periodontal disease (Group I), those with generalised chronic periodontitis (Group II), and those with widespread aggressive periodontitis (Group III). Male and female subjects were included in the research.

Fluffy flowers. Participation in the study is contingent upon the following exclusion criteria: systemic illness, current or past use of iron replacement therapy for anaemia, recent periodontal therapy, antibiotic or nonsteroidal anti-inflammatory drug use (NSAID) use within the three months prior to the study, severe osteoporosis, uncontrolled diabetes, immunosuppression, bleeding disorders, cancer, stroke, or any other medical condition. The study did not include individuals who were taking bisphosphonates, nursing mothers, those with autoimmune diseases, or who had received an organ transplant.

Up until recently, researchers paid little attention to the ways in which long-term dental issues impact overall health. Proposing periodontal infection as a likely risk factor for serious medical consequences is a paradigm shift in our knowledge of the relationship between oral and systemic diseases. A substantial and persistent gram-negative bacterial challenge is presented to the host by the subgingival microbiota in cases of periodontitis. Periodontal diseases are characterised by the presence of ulcerated or discontinuous sulcular epithelium and junctional epithelium, which allow bacteria and their metabolites easy access to the bloodstream. It follows that periodontitis is thought to be responsible for a mild systemic inflammation. The inflammation-induced anaemia is mediated by cytokines. Symptoms include hypoferramia, appropriate reticuloendotelial iron reserves, and ferritin concentrations ranging from normal to high; this condition is a hallmark of chronic inflammatory diseases. This is something that doctors often see in their patients. The periodontitis that might lead to anaemia, according to Hutter et al., can have long-lasting effects on the body as a whole. Numerous studies have shown that anaemia is more common in people who have chronic periodontitis. The expression of hepcidin and interleukin-6 during inflammation is thought to be the main factor that contributes to the development of anaemia in chronic diseases [15,16].

During their treatment, Vilela et al. found that individuals with chronic periodontitis and chronic renal impairment had lower serum prohepcidin levels. Serum levels of Interleukin-6 and Hepcidin were shown to be higher in patients with chronic periodontitis, according to a 2015 study by Carvalho et al. People with chronic periodontitis have never before had their Hepcidin levels tested.

Researchers Lin-Na Guo observed increased blood ferritin and hepcidin levels in patients with chronic periodontitis and chronic periodontitis in conjunction with type 2 diabetes mellitus in their 2018 study. Neither the blood hepcidin levels of aggressive periodontitis patients nor the efficacy of Phase 1 treatment in lowering these levels has been well investigated in the existing literature. We can use this to aid in our research.

For patients with chronic periodontitis, the initial levels of Hepcidin were measured at 13.99±1.24 and 60.54±2.15, while for healthy persons, the values were 18.65±2.84 and 68.04±2.99, respectively. Researchers found that IL-6 and Hepcidin levels were greater in people with chronic periodontitis compared to healthy participants, which is in line with what Carvalho et al. found in their 2015 study [17,18].

A higher concentration of Interleukin-6 (17.67±1.07) and Hepcidin (65.79±1.79) was found in aggressive periodontitis patients compared to healthy individuals. To compare the average baseline values of GBI, PPD, PI, IL-6, and Hepcidin among groups I, II, and III, a one-way analysis of variance (ANOVA) was used. According to the results, the differences were statistically significant with a p-value less than 0.05.  Compared to the baseline measurement of 81.36±6.29, the average GBI (Gingival Bleeding Index) for Group II after three months was 23.97±3.86. From the beginning to the end of the three-month period, the average GBI showed a substantial decline (p=0.000). The average plaque index score went from 2.66±0.21 at the start to 0.85±0.21 after three months. There was a statistically significant (p=0.000) change in plaque score between the baseline and three-month mark. The average postpartum depression (PPD) decreased from 6.79 ±0.42 at the start of the research to 3.86 ±0.48 after three months. From the first measurement to the three-month mark, there was a statistically significant decrease in PPD (p=0.000) [19,20].

Three months after the trial started, the average Glasgow Benefit Inventory (GBI) for Group III was 19.32±2.89, which is lower than the baseline value of 78.19±5.01. From the beginning to the end of the three months, the average GBI showed a distinct decline (p=0.000). Compared to the baseline level of 2.12±0.32, the average plaque index score dropped to 0.74±0.21 after three months. From the first point to three months, there was a very substantial statistical effect (p=0.000) in the average reduction of plaque score. From an initial score of 7.18±0.42, the average postpartum depression (PPD) decreased to 4.69±0.48 after three months. From the first measurement to the three-month mark, there was a statistically significant drop in PPD (p=0.000). Plaque index, gingival bleeding index, and pocket probing depth were all reduced in Groups II and III following three months of phase I treatment. This proves that non-surgical treatment is effective in enhancing periodontal health. Following the completion of the first three months of treatment, group II's average blood Hepcidin level dropped from 68.04±2.99 to 61.49±2.41. A statistically significant p-value of 0.000 indicates that the blood Hepcidin level decreased significantly between the baseline and three months. Consistent with the results given here, Guo et al. (2018) found that patients with chronic periodontitis whose treatment began with phase I had lower hepcidin levels. Compared to the initial level of 18.65±2.84, the average serum IL-6 level after three months was 13.87±1.21. An earlier study that looked at IL-6 levels in chronic periodontitis patients after Phase I treatment discovered that there was a significant drop in blood IL-6 levels between the first measurement and three months later, with a p-value of 0.000 [21,22].

Group III's average serum Hepcidin level was 60.42±1.99 after three months, a decrease from the beginning readings of 65.79±1.79. A statistically significant p-value of 0.000 indicates that the blood Hepcidin level decreased significantly between the baseline and three months. Initially, the trial began with an average serum IL-6 content of 17.67±1.07. It dropped to 13.41±0.79 after three months. Statistically significant (p=0.000) was the average decrease in IL-6 level between the first measurement and the three-month mark. There was no statistically significant reduction in systemic inflammatory markers observed after periodontal therapy, according to Ide et al. (2003). However, research has demonstrated that periodontal therapy can effectively lower a number of systemic inflammatory markers. Our results show that higher levels of Hepcidin and IL-6 are associated with periodontal disease. As group II and III's periodontal health improved, the levels declined. There were no statistically significant changes (p=0.225 and 0.193, respectively) between groups II and III in their mean 3-month IL-6 and Hepcidin readings. Chronic periodontitis patients had lower levels of IL-6 and Hepcidin as compared to healthy controls and patients with aggressive periodontitis. Patients with aggressive periodontitis and those with chronic periodontitis had slightly different levels of IL-6 and Hepcidin at the start and three months of Phase I treatment, but this difference was not statistically significant. The first phase of periodontal treatment was successful in both groups.

This study is the first of its kind to try to measure how much Hepcidin is present in patients with advanced periodontitis. The progression of chronic disease-related anaemia is regulated by hepcidin and IL-6. It is critical to evaluate the relationship between IL-6 and Hepcidin levels and periodontal disease [22–24].

Strong evidence suggests that periodontal disease is associated with anaemia and higher IL-6 levels in the blood. It appears that IL-6 levels are affected by periodontal disease treatment. As a result of the body's inflammatory reaction to treatment, IL-6 levels rise briefly; however, they fall thereafter as the periodontal disease improves clinically. No one has looked into the possibility that patient Hepcidin levels are related to how well phase I therapy for periodontitis works. Comparing healthy individuals to those with aggressive and long-term periodontitis, this study sought to measure serum levels of IL-6 and hepcidin. After the first phase of treatment, the levels were checked and adjusted for both groups. The results showed that both groups' periodontal health improved after phase I periodontal therapy, which successfully reduced IL-6 and hepcidin levels. Reducing the patient's risk of periodontal-related anaemia, the reduction of IL-6 and hepcidin levels in the bloodstream will improve their general health. Further research with larger samples is required to confirm the association between Hepcidin and periodontal disease

An infection with bacteria that persists over time is the main cause of periodontal disease, an inflammatory disorder with several manifestations. In response to an infection, the host immune system distributes a cascade of cytokines. Among these cytokines, IL-6 is one. The levels of interleukin-6 in the blood are higher in patients who have periodontitis. Increased levels of interleukin-6 in the blood can cause the liver to secrete more hepcidin, a protein involved in the acute phase. Inflammatory anaemia is mostly determined by hepcidin, according to most experts. Researchers have discovered a link between periodontal disease and anaemia in patients with elevated levels of hepcidin and IL-6. Deterioration of periodontal tissue occurs as a consequence of anaemia, which reduces oxygen delivery and increases oxidative stress in periodontal disease. Anaemia and periodontal disease are linked, as this shows. The evidence suggests that investigating the link between anaemia and gum disease is of the utmost importance.

This study set out to measure how much hepcidin and interleukin-6 are present in the blood of healthy people. In order to measure interleukin-6 and hepcidin levels in the blood of people who have chronic periodontitis. In order to measure interleukin-6 and hepcidin levels in the blood of people with advanced periodontitis. Comparing the blood levels of hepcidin and interleukin-6 in two groups—one with aggressive, chronic, and healthy periodontitis and the other without—is the main purpose of this research. Finding out how much hepcidin and interleukin-6 exist in the blood of people with chronic periodontitis before and after they have phase I periodontal therapy is the main goal of this research. Hepcidin and interleukin-6 serum concentrations in patients with advanced periodontitis will be measured before and after phase I periodontal therapy. This study aims to compare these levels. For the purpose of comparing the hepcidin and IL-6 levels in the blood serum of aggressive periodontitis patients to those of chronic periodontitis patients. A total of forty-five patients were divided into three equal groups, with fifteen patients in each. Patients with generalised chronic periodontitis made up Group II, healthy individuals made up Group I, and those with severe periodontitis across the board made up Group III. Clinical parameters, IL-6, and Hepcidin levels were measured at baseline and three months after phase I therapy in groups I, II, and III. Statistics were applied to the values.

The results of our investigation are presented here. The levels of IL-6 and Hepcidin were greater in the group of people diagnosed with chronic periodontitis as compared to the control group. The levels of IL-6 and Hepcidin were found to be lower in the control group when compared to individuals with severe periodontitis. Three months after the start of phase I treatment, there was a significant drop in IL-6 and hepcidin levels across the board. At baseline and three months following therapy, participants with aggressive or chronic periodontitis did not differ significantly in their levels of IL-6 or Hepcidin. Groups II and III reported significant improvements in all clinical parameters following phase I treatment. Hepcidin and IL-6 levels were also positively correlated with the improved clinical indicators. Serum levels of hepcidin and IL-6 were shown to be higher in individuals with severe and chronic periodontitis, as previously reported. Anaemia due to a chronic illness is more likely to occur in patients with elevated serum hepcidin and IL-6 levels. The periodontium (the tissues surrounding the teeth) may be more sensitive to local irritation under anaemic situations due to a decrease in oxygen reaching the tissues, which could lead to periodontal disease, according to numerous theories.

People with aggressive and chronic periodontitis saw a decrease in hepcidin and IL-6 levels after phase I therapy. An essential part of treating aggressive and chronic periodontitis, phase-I therapy successfully stops the progression of periodontal disease-related anaemia, improving the patient's overall health. The association between periodontal health and the patient's serum Hepcidin levels could be further validated by conducting more research with a larger sample size. Finding out whether there is a connection between IL-6 and Hepcidin levels in the blood and the start of periodontal disease is the main goal. In order to determine whether the phase I treatment was successful in lowering blood IL-6 and Hepcidin levels.

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