The balance of proinflammatory cytokines and Treg cells in chronic glomerulonephritis

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Abstract


Chronic glomerulonephritis (CGN) is a disease with a steadily progressing course, which is based on inflammation with the activation of immune cells. The severity of the inflammatory reaction in the kidney tissue is determined by the balance of locally pro-inflammatory factors and protective mechanisms, which include anti-inflammatory cytokines and T-regulatory lymphocytes (Treg). The study of processes that can modulate the severity of inflammation in the kidney is of particular interest for understanding the basic patterns of CGN progression.

Aim. To determine the clinical significance of the Th17, Th1, and Treg cytokines in urine to assess the activity and progression of chronic glomerulonephritis with nephrotic syndrome (NS).

Materials and methods. The study included 98 patients with CGN – 37 women and 61 men. Patients were divided into two groups according to the degree of CGN activity. Group I consisted of 51 patients with NS. In 21 subjects, a decrease in GFR<60 ml/min was revealed. Group II included 47 patients with proteinuria from 1 to 3 g/day without NS. GFR<60 ml/min/1.73 m2 was observed in 26 patients. A kidney biopsy was performed in 65 patients and the hystological diagnosis was verified: 20 had mesangioproliferative GN, 16 had membranous nephropathy, 18 had focal segmental glomerulosclerosis, and 11 had membranoproliferative GN. The control group consisted of 15 healthy people. The levels of IL-6, IL-10, IL-17, tumor necrosis factor a (TNF-a) in the urine were determined using enzyme-linked immunosorbent assay. The number of FoxP3-positive cells in the inflammatory interstitial infiltrate of the cortical layer was determined in 39 patients (in a biopsy sample in a 1.5 mm2 area).

Results. In group of patients with CGN, there was an increase in the levels of Th17, Th1, and Treg cytokines in urine – TNF-a and IL-10 compared with healthy individuals. An increase in the levels of IL-6 in the urine of patients with high clinical activity of CGN (with NS and renal dysfunction) was more pronounced than in patients with NS and normal renal function. There was a decrease in the number of Treg cells in the interstitium of the kidney and a decrease in the production of anti-inflammatory IL-10 in CGN patients with NS, compared with patients without NS. The most pronounced changes in the cytokine profile were observed in patients with FSGS with an increase in pro-inflammatory cytokines and a decrease in Treg in the kidney tissue/anti-inflammatory IL-10 in the urine.

Conclusion. An imbalance of cytokines characterized by an increased levels of pro-inflammatory IL-17, IL-6, TNF-a, and a reduced levels of anti-inflammatory IL-10 and T-regulatory cells in the kidney tissue is noted in patients with NS, especially with FSGS. Imbalance of cytokines reflects the high activity of CGN and the risk of the progression of the disease.


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About the authors

Natalya V. Chebotareva

Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: natasha_tcheb@mail.ru
ORCID iD: 0000-0003-2128-8560

Russian Federation, Moscow

д.м.н., проф., каф. внутренних, профессиональных болезней и ревматологии; Клиника ревматологии, нефрологии и профпатологии им. Е.М. Тареева

Anatoly A. Vinogradov

Lomonosov Moscow State University

Email: natasha_tcheb@mail.ru
ORCID iD: 0000-0001-7529-0215

Russian Federation, Moscow

клинический ординатор каф. внутренних болезней

Alla A. Gindis

Sechenov First Moscow State Medical University (Sechenov University)

Email: natasha_tcheb@mail.ru
ORCID iD: 0000-0002-3959-9482

Russian Federation, Moscow

к.м.н., межклиническая клинико-диагностическая лаб., врач

Irina N. Bobkova

Sechenov First Moscow State Medical University (Sechenov University)

Email: natasha_tcheb@mail.ru

Russian Federation, Moscow

д.м.н., проф. каф. внутренних, профессиональных болезней и ревматологии; Клиника ревматологии, нефрологии и профпатологии им. Е.М. Тареева

Wenjing Cao

Sechenov First Moscow State Medical University (Sechenov University)

Email: natasha_tcheb@mail.ru
ORCID iD: 0000-0003-2694-4547

Russian Federation, Moscow

аспирант каф. внутренних, профессиональных болезней и ревматологии; Клиника ревматологии, нефрологии и профпатологии им. Е.М. Тареева

Lidia V. Lysenko

Lomonosov Moscow State University

Email: natasha_tcheb@mail.ru
ORCID iD: 0000-0002-1166-7308

Russian Federation, Moscow

д.м.н. проф., каф. внутренних, профессиональных болезней и ревматологии, Клиника ревматологии, нефрологии и профпатологии им. Е.М. Тареева

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