To the issue of vagosympathetic balance assessment in patients with facial phlegmon

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Introduction

Recently, much attention has been paid to the functioning of the neuroendocrine-immune system, which significantly changes the severity of the inflammatory process. Thus, studies [1] have revealed that immunocompetent cells have receptors for acetylcholine, dopamine, enkephalins, and endorphins. On the one hand, leukocytes are capable of synthesizing neuropeptides. It has been established that patients with various inflammatory diseases have dysfunction of the autonomic nervous system (ANS), which can lead to hyperproduction of proinflammatory cytokines in response to specific antigens [2; 3]. An increase in energy consumption by the immune system during inflammation is due to an increase in systemic sympathetic activity [4]. On the other hand, parasympathetic dysfunction leads to a decrease in the activity of the Th1 response, which is necessary for an adequate inflammatory process and pathogen elimination [5]. Moreover, it has been shown that the effect of a number of drugs depends on the ANS response [6; 7].

In this regard, it is of interest to evaluate the number of different types of leukocytes and some biochemical parameters of the blood in patients with facial phlegmon and different types of autonomic nervous system. Among patients of dental hospitals, such an acute purulent process as facial phlegmon is often encountered. Earlier, we noted that such patients can be divided into two groups according to the severity of endogenous intoxication [8]. Probably, this situation can be caused by different types of the prevailing part of the autonomic nervous system.

The objective of the study is to assess the influence of the autonomic nervous system tone on the activity of the inflammatory process in facial phlegmon.

Materials and methods

For the study, a group of patients (mean age 49.8 ± 4.4 years) with facial phlegmon (n = 74) was divided into two groups based on the predominant type of ANS: "sympathotonics" (43 people, 45.5 ± 8.2 years) and "parasympathotonics" (31 people, 54.3 ± 6.7 years).

One of the indicators of the ANS balance is the Kerdo index (KI), which reflects the degree of influence of the parasympathetic nervous system on the cardiovascular system [8–10]. The Kerdo index was calculated using the formula: KI = (1 – (BP_diast/HR)) ´ ´ 100, where BP_diast is diastolic blood pressure; HR is heart rate [11].

To identify the dominant type of ANS the method of A.M. Vayne was used [11].

The peripheral blood samples were analyzed for leukocyte content and types by microscopic examination of Romanovsky-Giemsa stained preparations. Glucose concentration was determined by the glucose oxidase method (Russia), total protein by the biuret reaction (Russia), and C-reactive protein by the enzyme immunoassay (Russia). Optical density was measured using a plate spectrophotometer (PowerWave Bio-TEK Instruments, Inc.).

Statistical data processing was performed using the Statistica 7.0 package. The Shapiro-Wilk criterion was used to test the normality of the distribution.

In the case of a distribution close to normal, the Student t-test was used, in other cases, the Mann – Whitney criterion was used to assess the significance of differences. The results are presented as the mean and its error (M ± m).

Results and discussion

The conducted studies showed that patients with a predominance of the sympathetic nervous system are hospitalized longer (8.8 ± 0.3 days) than those with a predominance of the parasympathetic nervous system (7.9 ± 0.3 days; p = 0.03).

The study found that the peripheral blood of patients with facial phlegmon and prevailing sympathetic division of the ANS has an increased number of leukocytes (table). In addition, a comparative analysis of the cellular composition of blood leukocytes in patients with different types of ANS showed that with prevailing parasympathetic division, there are more band neutrophils and lymphocytes in the blood of such patients (see table).

 

The studied parameters in patients with facial phlegmon depending on the types of the autonomic nervous system

Parameter	Patients with prevailing sympathetic division, n = 43	Patients with prevailing parasympathetic division, n = 31	Reference values [12]	p between groups
Leukocytes, in 1 μL	11,300 ± 200	8,200 ± 600	4,000–9,000	0.001
Band neutrophils, %	5.0 ± 0.9	2.3 ± 0.9	1–6	0.047
Band neutrophils, in 1 μL	600 ± 100	200 ± 100	40–300	0.024
Segmented neutrophils, %	71.2 ± 4.3	76.7 ± 3.0	47–72	0.22
Segmented neutrophils, in 1 μL	8,000 ± 600	6,300 ± 600	2,000–5,500	0.06
Lymphocytes, %	23.8 ± 4.2	10.7 ± 1.2	19–37	0.03
Lymphocytes, in 1 μL	2,700 ± 400	900 ± 100	1,200–3,000	0.01
Monocytes, %	4.7 ± 0.8	7.3 ± 0.7	3–11	0.03
Monocytes, in 1 μL	500 ± 100	600 ± 80	90–600	0.31
Glucose, mmol/L	5.1 ± 0.3	6.2 ± 0.4	3.5–5.5	0.04
Total protein, g/L	69.0 ± 2.3	66.0 ± 2.0	65–85	0.22
CRP, mg/L	53.3 ± 5.1	86.7 ± 2.6	1.0–8.0	0.04

 

Among the biochemical parameters, the concentration of total protein did not differ significantly between the groups (p = 0.22). With prevailing parasympathetic division of the ANS, patients had a higher concentration of glucose in the blood serum than with hypersympathicotonia (p = 0.04). The concentration of C-reactive protein with prevailing parasympathetic system was significantly higher than with sympathicotonia (p = 0.04) (see table).

The studies showed that patients with different types of ANS have different laboratory signs of inflammation. In the case of hypersympathicotonia, there are more band neutrophils and lymphocytes in the blood, and the level of C-reactive protein is lower than in the group of "parasympathotonics". In general, leukocytosis in "sympathotonics" was due to an increase in all cell types, reaching the upper limits of reference values. On the other hand, with prevailing parasympathetic division of the ANS, the influence of hormones is insufficient to activate the inflammatory process. Studies [13] have found that with parasympathetic innervation through acetylcholine, the production of proinflammatory cytokines decreases, but does not change for IL-10, which partly explains the changes in the cellular composition of the blood in "parasympathotonics" observed in the present study.

It is known that changes in the activity of the ANS are associated with the action of products of activated inflammatory cells [14; 15]. In inflammatory tissues, the number of sympathetic fibers decreases, which leads to a decrease in anti-inflammatory signals and, together with the release of neuropeptides from sensitive nerve fibers, initiates and maintains local inflammation. In the acute phase of the process, such a configuration promotes release of the antigen, and in the chronic process, such changes lead to an unfavorable situation with a constant redistribution of energy and continuous local destruction [4; 16].

Lower concentrations of glucose and C-reactive protein in patients with hypersympathicotonia are probably due to faster catabolism in sympathicotonia. On the other hand, C-reactive protein in patients with prevailing sympathetic division of the ANS is spent on opsonization of microorganisms faster than in parasympathicotonia [17].

The results of this study, as well as literature data [18], suggest that regulation of ANS activity, especially the parasympathetic division, can be used as a therapeutic strategy to contain and prevent chronic inflammation. Activation of the cholinergic anti-inflammatory signaling pathway contributes to significant improvement in cytokine-mediated diseases such as sepsis, colitis, pancreatitis, and others [19].

Conclusions

1. In patients with facial phlegmon, leukocytosis is observed with sympathicotonia, while in "parasympathotonics" – lymphopenia without leukocytosis. In both cases, an increase in segmented neutrophils is determined.
2. Patients with prevailing sympathetic division of the ANS have a decrease in the level of C-reactive protein.
3. Changes in blood parameters depending on the dominant type of ANS must be taken into account when monitoring patients with facial phlegmon, when with prevailing parasympathetic division of the ANS there may not be an increase in leukocytes, which is necessary for an adequate assessment of the inflammatory process severity.

About the authors

I. A. Boev

E.A. Vagner Perm State Medical University

Author for correspondence.
Email: iosifboev@gmail.com
ORCID iD: 0000-0002-9682-7680

Degree Candidate of the Department of Dental Surgery and Maxillofacial Surgery, Dental Surgeon

Russian Federation, Perm

M. V. Yakovlev

E.A. Vagner Perm State Medical University

Email: iosifboev@gmail.com
ORCID iD: 0000-0002-2895-387X

Degree Candidate of the Department of Orthopedic Dentistry, Orthopedic Dentist

Perm

References

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