Научная статья на тему 'Changes cytokine spectrum in children with bronchopulmonary diseases with bronchial obstruction'

Changes cytokine spectrum in children with bronchopulmonary diseases with bronchial obstruction Текст научной статьи по специальности «Фундаментальная медицина»

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Ключевые слова
BRONCHOPULMONARY DISEASES WITH BRONCHIAL OBSTRUCTION / CYTOKINES / IMMUNE SYSTEM

Аннотация научной статьи по фундаментальной медицине, автор научной работы — Khaydarova Mukhtabar Mannapovna

In bronchopulmonary diseases with bronchial obstruction immune response develops mainly on Th-type, which suggests that in the occurrence of symptoms of bronchial obstruction, the leading role is played by the formation of the hearth of an infectious inflammation of the lung tissue. When analyzing the changes in the level of IL-4 in patients with ROB it has been found that the immune response feature is its Th-2 direction, which leads to overproduction of IgE and IgG. These processes ultimately determine the course and prognosis of the disease.

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Текст научной работы на тему «Changes cytokine spectrum in children with bronchopulmonary diseases with bronchial obstruction»

9. Delmaghani S., del Castillo F. J., Michel V. et al. Mutations in the gene encoding pejvakin, a 550 newly identifies protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy//Nature Genetics. - 2006. - 38: 770-778.

10. Attias J., Raveh E. Transient deafness in young candidates for cochlear implants//Audiol Neuro Otol. - 2007. - 12(5): 325-333.

Khaydarova Mukhtabar Mannapovna, Senior staff scientist of Republican Specialized Scientific and Practical Medical Center of Pediatric, Republic of Uzbekistan

E-mail: evovision@bk.ru

Changes cytokine spectrum in children with bronchopulmonary diseases with bronchial obstruction

Abstract: In bronchopulmonary diseases with bronchial obstruction immune response develops mainly on Th-type, which suggests that in the occurrence of symptoms of bronchial obstruction, the leading role is played by the formation of the hearth of an infectious inflammation of the lung tissue. When analyzing the changes in the level of IL-4 in patients with ROB it has been found that the immune response feature is its Th-2 direction, which leads to overproduction of IgE and IgG. These processes ultimately determine the course and prognosis of the disease.

Keywords: Bronchopulmonary diseases with bronchial obstruction, cytokines, immune system.

The development of the disease with immune pathogenetic basis should be considered from the point ofview of the effector parts of the immune system, which is involved in pathological processes is largely due to a cascade of cytokines. It is believed that when BO which the considered as a systemic inflammatory reaction cascade triggered by weight of pro-inflammatory and anti-inflammatory cytokines.

It is known that antigen entry into the body activates macrophages and causes secretion of a number of mediators, including IL-1p stimulating T cell proliferation and which is the main mediator of local inflammatory reaction, in any type of inflammation [1; 2; 3]. In addition, it is proved that the physiological conditions, IL-1 is able to increase the activity of Th1 cells by stimulating the secretion of IFN-y. Normally, the dominant form of secretion in humans is IL-1p [2].

IL-4 limits the incidence and intensity of inflammation, inhibits the production of pro-inflammatory IL-1p, activates B lymphocytes, increases the synthesis of immunoglobulin's primarily immunoglobulin G, E, contributing to the production of antibodies protective properties which neutralize the action of pathogenic agents. The development of the disease with immune pathogenetic basis should be considered from the point ofview of the effectors parts of the immune system, which is involved in pathological processes is largely due to a cascade of cytokines. It is believed that when BO which considered as a systemic inflammatory reaction cascade triggered by weight of pro-inflammatory and anti-inflammatory cytokines.

In order to characterize the functional state of the T1 and T2 have surveyed our children with bronchopulmonary pathology (BLP) with bronchial obstruction (BO) studied the features of production IL-1p and IL-4 in serum Peripheral blood.

Material and methods

We observed 371 children aged from 3 months up to 7 years: 110 of them to OB, 50 children with obstruktiv recurrent bronchitis flow (OBRT), BLP 211 patients with symptoms of OB and 20 healthy children.

When the diagnosis into account medical history, the results of clinical, radiographic, functional, biochemical, immunological and psychological research methods. Verification of the diagnosis based on the classification adopted in Moscow at the Symposium (on improving the classification of non-specific lung diseases in children, 1995).

Children have been subjected to clinical examination with the standard description of the personal data, including during

pregnancy, nutrition of pregnant and breastfeeding, childbirth, the neonatal period, the application timing to the chest, child nutrition in infancy transferred somatic diseases background state.

Results and its discussion

Our studies have shown that in healthy children IL-1^ products ranged from 14-69 pg/ml and the average stood at 52.4-3.5 pg/ml. Children with BLP, hypercytokinemia marked both by pro- and anti-inflammatory cytokine with a maximum concentration of IL-1p in patients with intense inflammation and adequately reflect the severity of their course.

A comparative analysis of the level of pro-inflammatory cytokine IL-1p, depending on the presence or absence of BO showed that when ON 1.3 times at OB 1.9 times and 2 times in the BPBO was increased in patients with BO. Study of anti-inflammatory indicators cytokine IL-4 showed an increase in their standard of 1.6 times, 2 times and 1.4 times at the BW in children with OB, OP, and RB, respectively.

We have found that in children with AOB production IL-1p was significantly (P < 0.01) increased to 125.8 ± 5.7 pg/mL compared with healthy children. In patients with BPBO indicator IL-1^ production was significantly (P < 0.01) increased to 286.2 ± 10.7 pg/ml, which was 5.4 times higher than the norm. Patients with OBRT index products IL-1^ succeed to 198.5 ± 21.2 pg/ml. These data suggest the presence of IL-1p depending on the level of production on the nature of the infectious process, as evidenced by the upconsciously high level of secretion in patients with OBRT. There regulation increase in proinflammatory interleukin IL-1p in all the surveyed groups, but it is more pronounced in case of acute pneumonia with obstructive syndrome, exceeding the norm by 5.4 times. We fixed that when AOB and OBRT their level increased by 2.4 and 2.3 times, respectively, that is, the severity of the changes of this indicator was practical the same in case of bronchitis.

The study showed that the increase in IL-4 takes place in all groups with the AOB, but it is most pronounced in patients with BPBO. If patients with acute process OBRT - IL-4 levels in serum increased by 3.2 and 3.3 times, respectively, the BPBO at 4.5 times. Intensive synthesis of IL-1^ and IL-4 at OBRT displays cytokine imbalance in the system. At the same time the immune response in patients with OP BO develops pre and property by Th-1-type,

Changes cytokine spectrum in children with bronchopulmonary diseases with bronchial obstruction

which suggests that in the occurrence of symptoms of bronchial obstruction, the leading role is played by the formation of the hearth in-infectious inflammation of the lung tissue.

A more significant increase in anti-inflammatory cytokine IL-4 compared to the pro-inflammatory IL-1p in the BPBO, and especially when OBRT indicates menen of immune re-sponse with a predominance of Th-2 responsible for the humoral immune response.

It should be noted that the production of both pro- and anti-inflammatory cytokine was greatest (significantly higher) with OBRT than without.

As the table shows, the level of proinflammatory cytokine IL-1p during repeat-term obstruction tended to decrease in all groups of patients, but remained above you — normative values of 1.5 times at AOB, 3.3 times in BPBO, 1.7 times at the OBRT. Analyzing the level of anti-inflammatory cytokines — IL-4, we found the opposite trend, namely a significant increase in this indicator compared to the previous obstruction. Consequently, the level of IL-4 continued to differ significantly from that of the norm of 4.9 times at AOB, 4.5 times in OBRT and 7.8 times at the ROB. From here, we can say that in the pathogenesis of BO is set to an imbalance in the cytokine system, in repeated cases, AOB plays a major role anti-inflammatory cytokines — IL-4.

The data show an increase in the blood serum of children with BLP proinflammatory cytokines — balance changes imunoregu-lyation mediators. Immunodeficiency's associated with disorders of immune regulation, lead to a weakening of the immune response controls, may lead to the development of autoimmune diseases against loss of immunological tolerance to self antigens and often the trigger element in the pathogenesis of diseases. Failures cytokine network and immune disorders in AOB, in all probability, cgjcj, exacerbate immune deficiency and the development or exacerbation of clinical symptoms.

Increasing the content of cytokines, cytokine activation system should be disregarded as an indicator of activity, disease progression, involvement in the pathological process of the immune system, its deregulation. Hyperproduction pro- and antiinflammatory cytokines is evidence of serious irregularities in the work of all parts of the immune system, the oppression of nonspecific and specific immune protection that affect the course of the underlying disease, requiring appropriate correction. The data show an increase in the blood serum of children with AOB proinflammatory cytokines — balance changes imunoregulyator mediators. immunodeficiency associated with disorders of immune regulation, lead to a weakening of the immune response controls, may lead to the development of autoimmune diseases against loss of immunological tolerance to self antigens and often the trigger element in the pathogenesis of diseases. Failures cytokine network and immune disorders in BPBO, in all probability, capacity exacerbate immune deficiency and the development or exacerbation of clinical symptoms.

Interesting data were obtained by analyzing the individual is - following results: the highest values of IL-4 are registered in children with severe pneumonia with AOB and BPBO.

The most important, in our view is the study of the relationship between the pro- and anti-inflammatory cytokines when OBRT. The level of IL-1p and IL-4 for cases in repeat bronchial obstruction presented in the table.

In the airway, there are two subpopulations of helper — Th-1 and Th-2. Development of the immune response in children is largely determined by the direction of differentiation of ThO-tion — lymphocyte subpopulation Th-1 and Th-2. Th-1 subtype secretes cytokines play an important role in the defense against bacterial and viral infections Institute. Under the Th-2 type facilitates the proliferation of mast cells, IgE production, differentiation, and survival of eosinophils entiation.

Determining the level of IL-4 in the serum of patients with OBRT is an actcial, since this cytokine plays a central role in the synthesis of immunoglobulin E. Therefore, we would also be interesting to study IgE levels, depending on the IL-4 production in patients with AOB and without the AOB.

The correlation analysis showed the presence of high direct correlation between blood levels of IgE and IL-4 in patients with OBRT (r = 0.57 at AOB, r = 0.62 in OBRT, and r = 0.69 at BPBO). The period ofre-obstruction characterized polarized higher content of IL-4 in the serum, which is correlated with the frequency of the obstruction. At the same time the level of IL-1p in the serum did not correlate with repeated cases of bronchial obstruction. The correlation analysis revealed a significant imbalance between the individual links of the immune system and chi-Tokin that defines a variety of clinical manifestations of bronchial obstructive at AOB in children. Due to the fact that the development of bronchial obstruction depends on the combined effects of many factors, the ratio ofwhich individually specific case, the average figures do not always accurately reflect the average picture of the disease.

Thus, among the pathogenetically relevant factors largely determined development and frequency of bronchial obstruction include increases in the serum anti-inflammatory cytokine IL-4 and IgE.

Identified immune system dysfunction, manifested in oppression cellular immunity, stimulation of some indicators of humoral immunity, rise IL-1.beta and IL-4, which promotes the overproduction of IgE, is pathogenetic basis for the development of bronchial obstruction in children with BLP. It is interesting data analysis of the immune response of patients, depending on the nosology of BLP with BO.

Conclusion

Thus, the results of the study once again urge the advisability of studying the immune status of patients to identify the characteristics of the formation of bronchial obstruction, followed by sound correction.

Table 1. - Interleukins level in patients with BLP re-BO (pg/ml)

Indicators Healthy kids AOB n = 110 BPBO n = 211 OBRT n = 50

IL-10 52.4 ± 3.5 125.8 ± 5.7*** 286 ± 10.7***AAA 118.5 ± 21.2**

78.6 ± 5.4***aaa 172.9 ± 9.3*** 89.1 ± 7.6***

IL-4 35.1 ± 114.5 ± 3.1*** 117.3 ± 5.2***AAA 157.3 ± 3.8***

172.0 ± 8.7***aaa 157.9 ± 6.5*** 273.8 ± 14.7***AAA

Note: numerator — in the primary obstruction in the denominator — in time in the repeat obstruction; * — the differences with respect to healthy children meaningful data (** — P < 0.01; *** — P < 0.001), A — the difference between thepermary and reobstruction significant (AAA — P < 0.001).

References:

1. Хайдарова М. М., Шамсиев Ф. М., Мусажанова Р. А., Мирзамухамедов Д. М. Применение иммуномодулина при лечении обструк-тивного бронхита у детей раннего возраста//Материалы Республиканской научно-практической конференции «Проблемы иммуннопатологии детского возраста. - 1998. - С. 107-110.

2. Шамсиев Ф. М., Хайдарова М. М., Мусажанова Р. А., Якубова О. Ш. Клинико-иммунологические особенности острой осложненной пневмонии у часто болеющих детей дошкольного возраста//Актуальные проблемы содействия нормальному росту и развитию детей. - Ташкент, 2006. - С. 185-186.

3. Хайдарова М. М., Шамсиев Ф. М., Асадова Г. У, Мусажанова Р. А., Нигматуллаева М. Х. Психологические особенности детей с бронхо-легочной патологией//Материалы Республиканской научно-практической конференции «Организационные и научные проблемы снижения младенческой и детской смертности». - Ташкент, 28 ноября 2006. - С. 143-146.

Khakimov Sherali Kuzievich, PhD in Medicine, Scientific Research Institute Traumatology and Orthopedics of the Republic of Uzbekistan, Tashkent city

E-mail: sher-fannel@mail.ru

The improvement of pectus excavatum repair results using differentiated tactics in children

Abstract: This report presents the results of the operative correction of the PE in 54 children aged from 5 to 15 years. In relation to the SCC elasticity degree and age of the patient there was performed the PE repair by D. Nuss procedure and in modification with application of a metal plate of the own construction. The obtained results show that thoracoplasty by D. Nuss due to PE is required when the sternocostal complex is still elastic. PE with worsening SCC elasticity required the thoraco-plasty in modification.

Keywords: children, chest, pectus excavatum elasticity, D. Nuss procedure.

Background

The deformation of the chest has various forms, the overwhelming majority of them is the pectus excavatum (PE) (90 %) [1; 2]. The treatment of children with PE remains to be significant and not to be resolved completely problem of the children orthopedics. This is confirmed by the high percent of unsatisfactory results of operative correction of PE, which are found in more than 30 % [1; 3]. While having diversity ofvarious methods for operative correction of PE the cosmetic effect seems not to be resolved problem completely.

Though the majority of the authors use the method of thoracoplasty by D. Nuss with the purpose of elimination of the PE, the orthopedic features of treatment remain without appropriate attention. It is quite logical, that the performance of the same method of thoracoplasty at different types and severity of the PE in the patients ofvarious age groups leads to the predispositions for occurrence of various postoperative complications which quite often result in unsatisfactory results of treatment at the long-term period [4].

The purpose of work was to improve results of operative correction of PE in children.

Materials and methods. In the Clinic of Scientific Research In-sttitute of Traumatology and orthopedics of the Ministry of Health 54 patients with PE at the age from 5 to 15 y. were operated during the period from 2009 to 2013. All patients were known about their cosmetic impairment and so, they had moral degradation. Because, patients and their parents were given their consent to perform the operative intervention, notably, they completed out the act about occurrence of any complaints during the operation.

These children were divided into three groups in relation to the degree of sternocostal complex elasticity (SCC). All patient was performed treatment with use of the SCC elasticity criteria (patent № DGU 02466) including the following parameters: the test of autocorrection, difference of chest excursion at a deep inspiration and expiration, "torsion" of the breast bone and the angle of steepness of the deformed ribs. On the basis of SCC elasticity degree there were formed groups of the patients, according to which the choice of a method of operative correction was made. For operative correction of the SCC we used our developed (2010) and made by firm ChM (Poland) metal plate (patent № FAP 00825).

The results of the study are devoted to research of all parameters data of SCC elasticity degree, which are shown in table 1.

Table 1. - Distribution of the children with PE by the SCC criteria elasticity degree (n = 54)

Criteria Elasticity degree Totally

Light degree of elasticity of the chest n = 27 Moderate degree of elasticity n = 15 Severe degree of hypoelastic chest n = 12

(TA) Test of autocorrection 27 (50.0 %) 17 (31.5 %) 10 (18.5 %) 54(100 %)

(CE) Excursion of the chest 28 (51.8 %) 15 (27.8 %) 11 (20.4 %) 54 (100 %)

(BBT) Breast bone torsion 27 (50.0 %) 15 (27.8 %) 12 (22.2 %) 54 (100 %)

Angle of the steepness of the deformed ribs 24(44.4 %) 20 (37.0 %) 10 (18.6 %) 54(100 %)

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