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"Child`s Health" 2 (45) 2013

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The role of α-defensins 1-3 in the formation of antimicrobial protection in children with recurrent bronchitis caused by bacteria of the genus Haemophillus

Authors: G.O. Lezhenko1, O.E. Abaturov2, O.E. Pashkova1, L.I. Pantyushenko3, 1 Zaporizhzhya State Medical Univescity, 2 SI «Dnipropetrovsk Medical Academy», 3 Zaporizhzhya State Clinical Childrens Hospital

Categories: Infectious diseases, Pediatrics/Neonatology, Pulmonology

Sections: Clinical researches

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Summary

The level of α-defensins 1–3 (HNP 1–3) has been analyzed in the blood plasma of children with recurrent bronchitis caused by bacteria of the genus Haemophilus. It is shown that the level of HNP 1–3 in the blood plasma depends on the form of Haemophilus. Trigger of HNP 1–3 outflow for neutrophils was the presence of bacterial capsule while presence of L-forms of Haemophilus influenzae wasn’t associated with increase in synthesis of antimicrobial peptides that could be one of the factors of forming of Haemophilus antibiotic resistance.

Досліджено рівень α-дефензинів 1–3 (HNP 1–3) у плазмі крові дітей, хворих на рецидивуючий бронхіт, викликаний бактеріями роду Haemophilus. Доведено, що рівень HNP 1–3 у плазмі крові залежить від форми Haemophilus. Тригером вивільнення HNP 1–3 із нейтрофілів є наявність капсули бактерії, у той час як наявність L-форм гемофільної палички не супроводжується підвищенням синтезу антимікробних пептидів, що може бути одним із факторів формування антибіотикорезистентності Haemophilus.

Исследован уровень α-дефензинов 1–3 (HNP 1–3) в плазме крови детей с рецидивирующим бронхитом, вызванным бактериями рода Haemophilus. Установлено, что уровень HNP 1–3 в плазме крови зависит от формы Haemophilus. Тригерром высвобождения HNP 1–3 из нейтрофилов является наличие капсулы бактерии, в то время как наличие L-форм гемофильной палочки не сопровождается повышением синтеза антимикробных пептидов, что может быть одним из факторов формирования антибиотикорезистентности Haemophilus.


Keywords

рецидивуючий бронхіт, α-дефензини 1–3, Haemophilus influenzae, діти.

рецидивирующий бронхит, α-дефензины 1–3, Haemophilus influenzae, дети.

recurrent bronchitis, α-defensins 1–3, Haemophilus influenzae, children.

The purpose of this investigation is to define the role of α-defensins 1-3 in forming of antimicrobial protection in children with recurrent bronchitis caused by bacteria of the genus Haemophillus.

In 68 children with recurrent bronchitis the bacteriological status was examined. It was found that in 47.1% of cases in children with recurrent bronchitis the colonization of respiratory tracts by Haemophilus influenzae was detected. For further observations we choose 32 children suffering from recurrent bronchitis  with isolated strains of Haemophilus influenzae during the bacteriological examination of their sputum. In 21 children (65.6%) the capsular strains and in 11 patients (34.4%)   the unencapsulated (L-shaped) strains of Haemophilus influenzae were found.

Investigation of α-defensins 1-3 content has revealed the plasma level of this antimicrobial peptide of 3583,3 ± 735,4 pg / ml in children from the control group in comparison to  group of children with recurrent bronchitis where the level of α-defensins 1-3 was almost twice fold increased consisting of 6576,7 ± 602,8 pg / ml, p <0.01. In patients where L-shaped forms of Haemophilus influenzae were found only the traces of HNP 1-3 in plasma were detected while the plasma concentration of α-defensins of patients in whom the capsular strains of Haemophilus influenzae during the bacteriological examination of sputum were detected this level was 1.9 times the value of the control group and consisted of 6766,7 ± 584,2 pg / ml. Thus, the presence of bacterial capsule acted as a trigger of HNP1-3 secretion from azurophilic granules of neutrophils.

During the study of serum cytokine profile it was found that in children with recurrent bronchitis the content of proinflammatory interleukin-6 had a tendency to increasing compared with the control group (10,1 ± 2,0 pg / ml vs. 9, 1 ± 1,1 pg / ml , respectively, p> 0.05), while the level of an anti-inflammatory interleukin-10 has increased three times more  consisting of 4,42 ± 1,0 pg / ml vs 1,41 ± 0.59 pg / ml, respectively (p <0.05). The lowest value of interleukin-6 and the highest value of interleukin-10 were observed in the presence of Haemophillus L-forms and by combining to abnormally low levels of α-defensins 1-3 it can serve as one of the antibacterial resistance development factors.

By the consideration of microbiological study results the cephalosporin II generation antibiotic in the therapy of children with recurrent bronchitis was included. Clinically the complete recovery to 7-th day of treatment with cephalosporin of II generation has been reached in 26 (81.2%) patients. In 6 children (18.8%) with L-shaped forms of Haemophilus influenzae during bacteriological investigation of sputum the recovery was incomplete due to presence of inferquent dry cough. It required a continuation of antibiotic therapy course up to 10-14 days and the additional prescribing of an immunomodulating drug that activates the defensins synthesis. After antibiotic therapy course, during control microbiological examination the pathogenic flora in significant concentrations was not detected in all the patients.

Conclusions:

  1. Haemophilus influenzae is leading etiologic factor in the recurrent acute bronchitis development in children. This fact is confirmed by a high colonization level of the respiratory tract consisting of 47.1%.
  2. The presence of capsular forms of Haemophilus influenzae accompanied by increased plasma levels of a-defensins 1-3 while isolating of L-forms of Haemophilus influenzae is accompanied by increased synthesis of antimicrobial peptides.
  3. In children with recurrent bronchitis an imbalance between pro-and anti-inflammatory cytokines takes place with revealing of serum interleukin-10 increased level against insufficient interleukin-6 production. The mentioned changes are the most significant in the presence of L-forms of Haemophillus influenzae.
  4.  Including of II generation cephalosporins in the treatment of recurrent bronchitis in children has demonstrated the high efficacy and safety against Haemophillus influenzae.
  5.  For the purpose of enhancing the antibacterial action of II generation cephalosporins and for induction of α-defensins plasma synthesis in the presence of Haemophillus L-forms the question about the additional prescribing of immune therapy should be considered.

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