Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome

AIMS: Investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C Motif Chemokine Ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes...

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Autores principales: E. V. Shikh, N. A. Petunina, L. V. Nedosugova, K. O. Galstyan, K. I. Kolmychkova, A. A. Makhova, Galin I. Gorodetskaya
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Publicado: Endocrinology Research Centre 2020
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Acceso en línea:https://doaj.org/article/88cb4542a9cf40a9a169a550921c30c7
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spelling oai:doaj.org-article:88cb4542a9cf40a9a169a550921c30c72021-11-14T09:00:23ZSpontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome2072-03512072-037810.14341/DM12343https://doaj.org/article/88cb4542a9cf40a9a169a550921c30c72020-08-01T00:00:00Zhttps://www.dia-endojournals.ru/jour/article/view/12343https://doaj.org/toc/2072-0351https://doaj.org/toc/2072-0378AIMS: Investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C Motif Chemokine Ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers and the effect of the course use of the combined metabolic drug Kokarnit as part of complex therapy on the dynamics of the severity of symptoms of DSPN and the cytokine phenotype in patients with long-term non-healing ulcers of the lower extremities MATERIALS AND METHODS: 121 patients with T2DM, 79 without diabetic foot syndrome (DFS) and 42 patients with DFS were included. CD14+ monocytes were isolated from patients’ blood and stimulated by interferon-γ (IFN-γ) and interleukine-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation in all patients before taking the combined metabolic drug Kokarnit. Then they were randomly allocated either to the control group (57 people), to whom Kokarnit was added to standard treatment, or to the comparison group. After a 9-day course of application of Kokarnit, the dynamics of indicators was evaluated on a TSS scale. Assessment of cytokine status was carried out in 18 people with long-term non-healing ulcerative defects of the lower extremities, on the first and ninth day of treatment. RESULTS: A correlation was found between HbA1c and levels of stimulated secretion of TNFα (r=0.726, p=0.027), CCL18 (r=-0.949, p=0.051) in patients with DSPN. In all patients with different duration of VDS, an increase in secretion of TNF-α and CCL18 was observed (p<0.05). However, stimulation of anti-inflammatory activation was not observed in patients with ulcerative defects lasting more than 6 months (p=0.033). The use of cocarnit in these patients had a decrease in stimulated secretion of TNFα and an increase in CCL18. Throughout the entire observation period with the therapy, the score for the symptoms of polyneuropathy on the TSS scale in patients of the control group was statistically significantly higher. CONCLUSION: Against the background of therapy in patients of the main group, a statistically significant dynamics of indicators on the TSS scale was established. The cytokine modulating ability of Kokarnit to switch the cytokine status into the category of anti-inflammatory.E. V. ShikhN. A. PetuninaL. V. NedosugovaK. O. GalstyanK. I. KolmychkovaA. A. MakhovaGalin I. GorodetskayaEndocrinology Research Centrearticletype 2 diabetes mellitusdiabetic foot syndrome (dfs)pro-inflammatory monocyte polarizationanti-inflammatory monocyte polarizationkokarniteNutritional diseases. Deficiency diseasesRC620-627ENRUСахарный диабет, Vol 23, Iss 3, Pp 210-222 (2020)
institution DOAJ
collection DOAJ
language EN
RU
topic type 2 diabetes mellitus
diabetic foot syndrome (dfs)
pro-inflammatory monocyte polarization
anti-inflammatory monocyte polarization
kokarnite
Nutritional diseases. Deficiency diseases
RC620-627
spellingShingle type 2 diabetes mellitus
diabetic foot syndrome (dfs)
pro-inflammatory monocyte polarization
anti-inflammatory monocyte polarization
kokarnite
Nutritional diseases. Deficiency diseases
RC620-627
E. V. Shikh
N. A. Petunina
L. V. Nedosugova
K. O. Galstyan
K. I. Kolmychkova
A. A. Makhova
Galin I. Gorodetskaya
Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome
description AIMS: Investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C Motif Chemokine Ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers and the effect of the course use of the combined metabolic drug Kokarnit as part of complex therapy on the dynamics of the severity of symptoms of DSPN and the cytokine phenotype in patients with long-term non-healing ulcers of the lower extremities MATERIALS AND METHODS: 121 patients with T2DM, 79 without diabetic foot syndrome (DFS) and 42 patients with DFS were included. CD14+ monocytes were isolated from patients’ blood and stimulated by interferon-γ (IFN-γ) and interleukine-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation in all patients before taking the combined metabolic drug Kokarnit. Then they were randomly allocated either to the control group (57 people), to whom Kokarnit was added to standard treatment, or to the comparison group. After a 9-day course of application of Kokarnit, the dynamics of indicators was evaluated on a TSS scale. Assessment of cytokine status was carried out in 18 people with long-term non-healing ulcerative defects of the lower extremities, on the first and ninth day of treatment. RESULTS: A correlation was found between HbA1c and levels of stimulated secretion of TNFα (r=0.726, p=0.027), CCL18 (r=-0.949, p=0.051) in patients with DSPN. In all patients with different duration of VDS, an increase in secretion of TNF-α and CCL18 was observed (p<0.05). However, stimulation of anti-inflammatory activation was not observed in patients with ulcerative defects lasting more than 6 months (p=0.033). The use of cocarnit in these patients had a decrease in stimulated secretion of TNFα and an increase in CCL18. Throughout the entire observation period with the therapy, the score for the symptoms of polyneuropathy on the TSS scale in patients of the control group was statistically significantly higher. CONCLUSION: Against the background of therapy in patients of the main group, a statistically significant dynamics of indicators on the TSS scale was established. The cytokine modulating ability of Kokarnit to switch the cytokine status into the category of anti-inflammatory.
format article
author E. V. Shikh
N. A. Petunina
L. V. Nedosugova
K. O. Galstyan
K. I. Kolmychkova
A. A. Makhova
Galin I. Gorodetskaya
author_facet E. V. Shikh
N. A. Petunina
L. V. Nedosugova
K. O. Galstyan
K. I. Kolmychkova
A. A. Makhova
Galin I. Gorodetskaya
author_sort E. V. Shikh
title Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome
title_short Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome
title_full Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome
title_fullStr Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome
title_full_unstemmed Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome
title_sort spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome
publisher Endocrinology Research Centre
publishDate 2020
url https://doaj.org/article/88cb4542a9cf40a9a169a550921c30c7
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