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ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 3  |  Page : 909-913

Interleukin-6 levels in the serum and saliva in patients with oral lichen planus


1 Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission24-Mar-2020
Date of Decision15-Apr-2020
Date of Acceptance15-Apr-2020
Date of Web Publication18-Oct-2021

Correspondence Address:
Shaymaa A. E Abd Elatef
Al Delengat, Al Beheira 22762
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_64_20

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  Abstract 


Background
Oral lichen planus (OLP) is a chronic inflammatory and autoimmune disease that affects ~1.9–4% of the population. It occurs more frequently in women, and the immunological system is believed to play a significant role in it. Interleukin-6 (IL-6) is a cytokine that contributes to the pathogenesis of OLP.
Objectives
The objective of the study is to evaluate IL-6 levels in the serum and saliva in patients of OLP compared with healthy controls, aiming to help in the future treatments of OLP.
Patients and methods
This case–control study was conducted on 20 patients with OLP, and 20 age-matched and sex-matched healthy volunteers, as a control group.
Results
The results have shown that there was highly statistically significant difference between groups regarding serum IL-6 levels with higher levels among cases (P < 0.001).
Conclusion
Higher levels of IL-6 in the saliva compared with the serum suggest that measurement of this marker in the saliva may be more useful than the serum for diagnostic and therapeutic aims.

Keywords: case–control, immunological, interleukin-6, oral lichen planus


How to cite this article:
Basha MA, Abd Elatef SA, El Gayed EM. Interleukin-6 levels in the serum and saliva in patients with oral lichen planus. Menoufia Med J 2021;34:909-13

How to cite this URL:
Basha MA, Abd Elatef SA, El Gayed EM. Interleukin-6 levels in the serum and saliva in patients with oral lichen planus. Menoufia Med J [serial online] 2021 [cited 2024 Mar 29];34:909-13. Available from: http://www.mmj.eg.net/text.asp?2021/34/3/909/328344




  Introduction Top


Oral lichen planus (OLP) is a chronic inflammatory and autoimmune disease that affects ~1.9–4% of the population. It occurs more frequently in women and the immunological system is believed to play a significant role in it [1]. OLP can be the sole clinical presentation of the disease or accompanied by cutaneous or other mucosal manifestations including the genital area, gastrointestinal tract, and the eyes [2].

Different forms, such as white striations, white plaques, erythema, ulcers, and blisters can be seen in the clinical features of OLP.

For better evaluation Sugerman and Savage [3] divided OLP simply into reticular and erosive.

This autoimmune disorder is mediated by T cells that locally present in the involved tissue release cytokines like interleukin-6 (IL-6), which contributes to the pathogenesis of OLP. IL-6 has been associated with multidrug resistance protein (MRP) expression by keratinocytes that upregulate MRP expression seen in OLP lesions [4].

IL-6 is generated by activated monocytes, macrophages, endothelial cells, and activated T and B cells that respond to a variety of stimuli, including infection and trauma [5].

Other immunological activities of IL-6 include B-cell differentiation and stimulation of immunoglobulin G secretion, T-cell differentiation and growth, and cytotoxic T-cell differentiation.

The levels of IL-6 increase in the serum of patients with malignant lesions. This IL inactivates the p53 tumor suppressor gene [6], promotes tumor cell proliferation, and increases the development and progression of some cancers such as oral squamous cell carcinoma [7].

Therefore, the levels of IL-6 in the serum and saliva of OLP patients are considered as reliable indicators of therapeutic response on a molecular basis [4].

There are many medications for OLP, but they are not sufficient for treatment. Numerous studies have identified that the IL-6 concentration in the serum of LP patients was higher than that in the healthy control, particularly in the severe forms of LP. Furthermore, serum IL-6 concentrations were identified to be particularly valuable for monitoring disease activity and treatment response [8]. The aim of this study is to evaluate IL-6 levels in the serum and saliva in patients of OLP compared with healthy controls, and hoping that it will help in the future treatments of OLP.


  Patients and methods Top


This case–control study was conducted on 20 unrelated patients with OLP, and 20 age-matched and sex-matched healthy volunteers, who have no present, past, or family history of OLP, as a control group. This study was approved by the Menoufia University Ethics Committee. The study was conducted from December 2018 to October 2019. A written informed consent was taken from all participants after informing them about the study.

This study had been conducted on 40 individuals who were divided into: group A (the patient group), consisting of 20 patients with OLP. Group B (control group): consists of 20 apparently healthy age-matched and sex-matched individuals. Inclusion criteria: all patients with OLP without systemic treatment 3 months before the study. Exclusion criteria: Patients of any dermatological disease other than OLP, smoking, diabetes mellitus, patients of any systemic autoimmune disease, and patients with malignancy.

A sheet was performed for all patients included in this study, including personal history such as name, age, sex, residence, occupation, and socioeconomic level; history of present illness: OLP history as well as history of other skin diseases or medications; history of drug intake: topical, systemic, or both; and history of systemic disease such as diabetes mellitus and HTP.

Regarding the onset, duration and course for patients group pain, it was assessed during exacerbation times, by present pain intensity of The McGill Pain Questionnaire [9].

The Pain Rating Index can be scored in several ways: 'Pain Rating Index – rank value': the adjectives are ranked according to increasing intensity so that each descriptor can be assigned a higher score, 'Pain Rating Index – scale value (visual analog scale)': the pain intensity of each pain descriptor was assessed on a numeric scale in previous research. The assigned rating can also be accepted as the score for the pain descriptor and 'number of words chosen': the number of words chosen by the patient. The higher the total score on the McGill Pain Questionnaire, the more the pain experience for the patient.

A complete clinical assessment of OLP lesions was done during exacerbation according to the clinical severity of OLP lesion.

Informed consent was obtained from all participants after being informed about the aims and process of the study as well as applicable objectives. The study procedures were free from any harmful effects on the participants as well as the service provided. The principal investigators have kept individual data as private information safely. There was no extra fee to be paid by the participants and the investigators covered all the costs in this regard.

Statistical analysis

Data entry, processing, and statistical analysis were carried out using MedCalc ver. 18.2.1 (MedCalc, Ostend, Belgium). Tests of significance (Kruskal–Wallis, Wilcoxon's, c2, logistic regression analysis, and Spearman's correlation) were used. Data were presented and suitable analysis was done according to the type of data (parametric and nonparametric) obtained for each variable. P values less than 0.05 (5%) was considered to be statistically significant.


  Results Top


There was no significant difference between groups regarding age. The mean ± SD ages of patients and controls were 51.7 ± 19.6 and 53.8 ± 18.3 years, respectively. Out of the 20 patients, 23 (15%) were men and 17 (85%) were women, whereas six (30%) members of the control group were men and 14 (70%) were women. There was no significant difference between groups regarding sex. So the patient and control groups were age, sex, and BMI matched [Table 1].
Table 1: Demographic and baseline characteristics of the study population

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There was highly statistical significant difference between groups regarding serum IL-6 levels with higher level among cases (P < 0.001) [Table 2].
Table 2: Comparison between the two studied groups according to serum interleukin-6 Levels

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There was highly statistically significant difference between groups regarding salivary IL-6 Levels with higher level among cases (P < 0.001) [Table 3].
Table 3: Comparison between the two studied groups according to salivary interleukin-6 levels

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In 20 patients ulcerative OLP (40%) was the most common type of OLP followed by reticular OLP (30%) [Table 4].
Table 4: Clinical type of oral lichen planus among the studied groups

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There was significant positive correlation between the levels of salivary IL-6 and OLP clinical type, P value less than 0.05 among the studied patients [Table 5].
Table 5: Correlation between levels of salivary interleukin-6 and oral lichen planus clinical type among the studied patients

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  Discussion Top


OLP is a chronic inflammatory subtype of LP that affect 1.9–4% of population [1].

IL-6 has been associated with MRP expression by keratinocytes that upregulate MRP expression seen in OLP lesions. Other immunological activities of IL-6 include B-cell differentiation and stimulation of immunoglobulin G secretion, T-cell differentiation and growth, and cytotoxic T-cell differentiation [10].

Numerous studies have identified that the IL-6 concentration in the serum of LP patients was higher than that in the healthy controls, particularly in severe forms of LP. Furthermore, serum IL-6 concentrations were identified to be particularly valuable for monitoring disease activity and treatment response [8].

The aim of this study is to evaluate IL-6 levels in the serum and saliva in patients of OLP compared with healthy controls, and hoping that it will help in the future treatments of OLP.

This case–control study was conducted on 20 unrelated patients with OLP, and 20 age-matched and sex-matched healthy volunteers, as a control group.

Findings of the study revealed that the mean age of participant's cases was 51.7 ± 19.6 years, and there was no statistically significant difference between two groups, and majority of cases were women and there was no statistically significant difference between case and control groups.

In agreement with this study, the study of AghaHosseini et al. [11] revealed that the mean age of participant cases is 37.4 ± 9.5 years, and there was no statistical difference between both case and control groups regarding age and sex.

IL-6 is a type of proinflammatory cytokine produced in LP lesions that exert effects on humoral and cellular immunities. It promotes B-cell differentiation, stimulates immunoglobulin G secretion, T-cell growth and differentiation, and cytotoxic T-cell differentiation. IL-6 is generated by activated monocytes, macrophages, endothelial cells, and activated T and B cells that respond to a variety of stimuli, including infection and trauma [12].

The present study assessed the serum level of IL-6 among participants and found that mean ± SD of it among cases is 3.76 ± 8.17 and 1.83 ± 1.42 among the control group and there was highly statistically significant difference between groups regarding to serum IL-6 levels.

Certain studies identified an increased serum IL-6 level in LP patients when compared with control groups [12].

In addition, a decreased serum IL-6 concentration was identified in LP patients subsequent to therapy [11].

Furthermore, it has been found that higher salivary IL-6 levels may primarily be due to keratinocytes, tissue-infiltrating mononuclear cells, and fibroblasts of LP lesions. The elevated serum IL-6 concentration may primarily be due to peripheral blood mononuclear cells and endothelial cells. The locally secreted IL-6 may diffuse into blood capillaries or be drained into the lymphatic vessels, which finally empty into the blood circulation. Together, the locally secreted IL-6 and the systemically produced IL-6 by peripheral blood mononuclear cells and endothelial cells are the possible reason for the elevated serum IL-6 concentration in LP patients [13].

Increased salivary concentrations of cytokines in OLP patients might be attributed to their increased release by the inflammatory cells or keratinocytes. On the other hand, injured oral mucosa (particularly in erosive LP) can no longer act as a protective barrier and this issue may also contribute to the increase in salivary levels of cytokines. Salivary IL-6 levels have been reported as elevated IL-6 levels in OLP patients by many authors; however, some authors reported decreased levels [14].

Sosroseno et al. [15] presumed that increased IL-6 levels develop simultaneously with presentation of autoantigens to the Langerhans cells. Therefore, IL-6 might modulate the severity of the oral lichen disease. Higher salivary IL-6 levels might reflect local or systemic production within many cell types; however, as cytokines act mainly locally and shortly it is more probable that their increased levels reflect local production from keratinocytes, monocytes, macrophages, activated T lymphocytes, endothelial cells, and fibroblasts.

Abdel-Haq et al. [16] reported that salivary IL-6 levels were increased in patients with OLP in comparison to healthy controls. Furthermore, patients with atrophic-erosive OLP had significantly higher IL-6 concentrations in their saliva compared with patients with reticular form of disease. The same authors concluded that the differences observed in IL-6 levels in patients with erosive-atrophic forms of OLP may indicate a substantial role played by the cytokine in the disease.

Gu et al. [17] detected elevated levels of oral and serum IL-6 in patients with ulcerative lichen in comparison to reticular lichen and controls, thus suggesting that elevated IL-6 might reflect chronic inflammatory nature of ulcerative lichen. On the contrary, Fayyazi et al. [18] suggested that OLP is a delayed type of hypersensitivity reaction in which cytokines (including IL-6) control proliferation and differentiation of cytotoxic T lymphocytes which attack the epidermis and lead to apoptosis of undifferentiated keratinocytes.

OLP is a chronic inflammatory disease of the oral mucosa the etiology of which is still unknown, but mounting evidence points to the immunologic basis of this disorder. Various causal factors have been associated with this disease, among such factors are: anxiety, diabetes, autoimmune diseases, mainly chronic liver disease, intestinal diseases, increased cholesterol, medications, stress, hypertension, infections, contact with dental materials, cancer, and a genetic predisposition to cancer [19]. Finally, a histopathological study must be performed in order to enable us to confirm the diagnosis [20].

OLP has many different forms; however, reticular type is the most frequent one [21]. In this study, we found that ulcerative OLP (40%) was the most common type of OLP followed by reticular OLP (30%) and the most affected site being the left buccal mucosa (80%).

The study of Gu et al. [17] evaluated 20 OLP patients for IL-6 levels: 10 with erosive OLP and 10 with reticular OLP. The IL-6 level was significantly higher in both oral exfoliated cells and serum in patients with ulcerative OLP compared with patients with reticular OLP (two patients with ulcerative OLP were in a very active disease phase so their serum IL-6 levels were greater than 100 pg/ml and deleting the two cases did not change the trend). This could be due to local and systemic production of IL-6 by many cell types. Therefore, IL-6 levels may change in types of OLP and with the severity of OLP.

Since 30–50% of patients with oral lesions also have cutaneous lesions, the presence of these characteristic cutaneous lesions can aid in the diagnosis of OLP. Several types of OLP have been described, the two main types being reticular and erosive OLP. It is not uncommon for the same patient to present with multiple forms of OLP [22].

In the oral cavity, the disease assumes somewhat different clinical appearance than on the skin, and is characterized by lesions consisting of radiating white, gray, velvety, thread-like papules in a linear, annular, and retiform arrangement forming typical lacy, reticular patches, rings, and streaks. A tiny white elevated dot is present at the intersection of white lines known here as striae of Wickham as compared with Wickham striae in the skin [23].

Additionally, the present study showed that there was significant positive correlation between the levels of salivary IL-6 and OLP clinical type, P value less than 0.05 among the studied patients. Also, there was significant positive correlation between the levels of serum IL-6 and OLP clinical type, P value less than 0.05 among the studied patients.

Of possible significance, elevated concentrations of IL-6 in the saliva and serum of patients with the erosive-atrophic form of OLP suggest that they may be involved in the etiology of this disease variation [16].

Rhodus et al. [24] supported a significant increased level of IL-6 in patients with OLP and a positive correlation between increased serum and salivary IL-6 levels and clinical forms of OLP lesions [21].

The Yin et al. [13] study showed a distinct association between the concentrations of IL-6 and LP was identified during the total combined analysis. These results indicated that IL-6 serum levels were significantly higher in patients with OLP than in the control group patients.


  Conclusion Top


The higher levels of IL-6 in the saliva compared with serum suggest that measurement of this marker in the saliva may be more useful than the serum for diagnostic and therapeutic aims of OLP.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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