RU2258504C1 - Agent for correction of disturbance in producing cytokines and markers for immune system cell activation in chronic iron-deficient anemia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention proposes an agent for correction of disturbances in production of cytokines and markers of activation of immune system cells in chronic iron-deficient anemia. Agent represents Sorbifer Durules known early as preparation used in treatment of iron-deficient anemia. Invention provides recovering the level of anti-inflammatory cytokines (IL-1, IL-6, IL-8, FNO-α, INF-α and INF-γ) and normalization of cellular immunity by indices of markers CD-25, CD-71 and CD-34.

EFFECT: valuable medicinal properties of agent.

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Description

The invention relates to medicine, namely hematology, and can be used to correct violations of the production of key cytokines and indicators of markers of activation of the immune system that develop in chronic iron deficiency anemia (IDA).

It is known that with IDA, secondary immune deficiency develops in the form of changes in indicators of nonspecific resistance, cellular and humoral immunity, a number of cytokines (Chepurnaya A.N. Immune disorders in iron deficiency anemia / Materials of the Russian scientific-practical conference "Actual problems of hematology and transfusiology", St. Petersburg, 2002 .-- p.178).

The prototype of this invention is the use of a stimulator of α-interferon-curantyl 300 mg 2 times a week for 2 months on the background of iron preparations. Its use is based on the ability of chimes to activate interferon production by leukocytes (Zyubina L. Yu. Pathogenesis, clinical picture, diagnosis and treatment of visceral lesions in iron deficiency conditions. Abstract. Thesis. Dr. Pa. Medical Sciences. - Novosibirsk, 2000. - 57 p.) . During treatment, only a slight increase in the level of INF-a was obtained, although the number of cases of infectious morbidity decreased by half.

There is a method of treating chronic iron deficiency anemia with iron preparations that have a substitute effect when it is deficient in the body (Iron deficiency anemia / Butler L.I. // Newdiamed-AO.-M, 1998.- 37 C.), as well as secondary immune deficiency, in the form of normalization of T-lymphocyte indices with persisting B-helper deficiency (Analysis of immunity indices in patients with IDA / Videborets SV // Medical business. - 2000. - Issue 3-4. - 71-75 s).

However, a comprehensive study of the effect of the iron preparation Sorbifer Durules in adequate dosages on the level of production of key cytokines (IL-1, IL-6, IL-8, FNO-α INF-α, INF-γ) and indicators of markers of immune system activation in IDA not given, which does not allow to sufficiently assess the state of the immune system in the course of therapy.

EFFECT: expansion of the arsenal of means for correcting the level of production of key cytokines and indicators of markers of activation of the immune system in the treatment of IDA patients. The specified technical result is achieved by the use of Sorbifer Durules as a corrector for these violations in IDA.

To correct the level of production of key cytokines and indicators of markers of activation of the immune system, the drug Sorbifer Durules (approved by the pharmacological committee of the Ministry of Health of the Russian Federation on September 29, 1999, registration number 011414/01 - 1999) is prescribed 1 tablet 2 times a day (daily dose of 200 mg of elemental iron ) for 3 months and 3 months of maintenance treatment, 1 t / day 10 days after menstruation, provided that the cause of the disease is eliminated. The studied parameters were studied before and in the dynamics of treatment (after 3 weeks of treatment).

The use of this drug in 102 patients with chronic IDA (severe - 50 (49.9%); moderate - 52 (51.9%) made it possible to practically restore the level of production of the studied cytokines by the first month of treatment (p> 0.05 with respect to the control) (Table 1) and indicators of the markers of activation of the immune system (Table 2). INF-α, FNO-α were the most sensitive to iron deficiency, since their parameters restored more slowly and had a significant correlation with the level of serum iron (r = -0.33 s IL-1, r = -0.39 s FNO-α, p> 0.05).

Clinical example: Patient Salimgareeva N.Ya., 53 years old, Russian by nationality, was in the hematology department of the RCH since 02.16.2002, No. medical. cards 201063. Address: RB, Baltachevsky district, the village of Starobaltachevo, st. Central 88. Does not work, education - incomplete secondary.

The clinical diagnosis is severe posthemorrhagic iron deficiency anemia. Sop. Vegetovascular dystonia with cardiological syndrome.

Complaints of weakness, dizziness, palpitations, inconsistent aching, pressing pains in the region of the heart, shortness of breath with moderate physical exertion, dry skin, hair loss, brittle and striated nails, periodically bites in the corners of the mouth, likes to eat dough, chalk. The patient considers himself since 1997 (24 years). The diagnosis was established since 1979. It was not regularly treated, with iron preparations from 2-3 weeks to 2 months, with long interruptions, notes the unstable effect of the treatment. She was born the 4th child in a row. Menses from 16 years old, regular, profuse, with clots, for 7-9 days, pregnancies - 6, childbirth - 3, abortion - 3, lactation of 1.5-2 g. There were no bleeding, blood transfusions. Currently, menopause for 5 years. Nutrition is balanced. Of the past diseases, SARS notes 2-3 times a year, pneumonia in 2000, tonsillitis in 2001.

Objectively: a state of moderate severity, the skin is pale, dry. Spoon-shaped nail plates, koilonychia. In the oral cavity - atrophy of the papillae of the tongue, tooth decay. Vesicular respiration over the lungs, heart rate 84 per minute, blood pressure 120 and 75 mm RT. Art. The abdomen is soft, moderately painful in the epigastrium, gastroduodenal zone; the liver and spleen are not enlarged, from the genitourinary system without deviations from the norm.

Laboratory examination data before and after treatment (indicators in dynamics are presented in brackets).

Complete blood count: erythrocytes - 4.4 · 10 ¹² / l (4.7 · 10 ¹² / l), hemoglobin -63 g / l (98 g / l), MCV - 60 (86.3), MCH - 20 (22.8), MCHC - 335 (264), leukocytes - 7.6 · 10 ⁹ / l (3.5 · 10 ⁹ / l), platelets - 300000 (268000), neutrophils: stab 1 (2), segmented 65 (75), lymphocytes 29 (18), monocytes 4 (4)%, ESR - 2 mm / hour (6 mm / hour).

Biochemical blood test: total protein - 79 g / l. Albumins - 57.5%, Globulins: α1 - 3.6, α2 - 8.0, β - 10.1, γ - 20.6%, Urea - 4.7 μmol / L, creatinine - 0.09 μmol / l, bilirubin - 10.8 μmol / l, ACT - 0.10 u / l, ALT - 0.20 u / l, thymol sample - 5.9, serum iron - 3.6 μmol / l. (16.6 μmol / L.), Ferritin - 6.3 ng / ml. (8.8 ng / ml.)

Immunogram: white blood cells - 8.21 · 10 ⁹ / l (6.1 · 10 ⁹ / l), lymphocytes - 2.2 · 10 ⁹ / l (3.07 · 10 ⁹ / l), lymphocytes - 27% (38 ), viability - 3% (4%), T-L - 65% (52%), T-L - 1.43 · 10 ⁹ / L (1.6 · 10 ⁹ / L), T-active - 13 % (11%), V-l - 0.13 · 10 ⁹ / l (0.18 · 10 ⁹ / l), V-l - 6 (8), Ig G - 13.2 (14.7), Ig A - 1.4 (1.3), Ig M - 1.2 (0.99), CEC - 65 (61), phagocytosis 43% (42%), phagocytic number - 4.1 (3.8), Comp. . - 83 (63).

Phenotyping: CD3 - 59, CD4 - 32 (30), CD8 - 21 (21), CD16 - 5 (7), CD25 - 9 (9), CD34 - 0 (0), CD71 - 3 (2), CD95 - 55 (53), HLA-DR - 43 (21).

Cytokines (pg / ml): IL1 - 512 (303), IL6 - 540 (271), IL8 - 1743 (891), FNOα - 462 (209) INFα 21 (74), INFγ - 108 (97, respectively).

Urinalysis: color - straw yellow, transparent, acid reaction, protein - negative, sediment - 0-1-2 epithelial cells. HC - 1013. Analysis by Nechiporenko - white blood cells 500 in 1 ml, red blood cells 250 in 1 ml.

Gregersen's reaction and analysis of feces for the presence of worm eggs is negative.

The conclusion of fibrogastroscopy: atrophic gastritis.

Chest x-ray: - chest organs without pathology.

Electrocardiogram: sinus rhythm, heart rate 81 per minute, pronounced dystrophic changes in the myocardium.

Ultrasound of the abdominal cavity, retroperitoneal space and pelvis: liver sizes within normal limits, echogenicity is diffuse-heterogeneous, pathological changes from the remaining organs of the abdominal cavity and small pelvis were not detected.

Gynecologist consultation: there are no gynecological diseases. Endocrinologist: endemic goiter 2 tbsp., Without impaired function.

Cardiologist: vegetovascular dystonia with tachycardial syndrome.

In order to correct iron deficiency, Sorbifer Durules was prescribed 2 tablets 2 times for 3 months, followed by taking maintenance doses for 10 days every month for 3 months.

During dynamic observation, the patient's condition improved, after 1, 3, 6 months, the hemoglobin level was - 105 - 118 - 126 g / l, serum iron - 18-20-21 μmol / l, ferritin - 9.8-11-12.6 ng / ml, there were no cases of infectious morbidity.

Thus, there is a long, neglected course of the disease due to chronic uterine hemorrhage, repeated pregnancies, childbirth, abortion, prolonged lactation, insufficient awareness of the patient, as well as inadequately conducted therapy, lack of control over the course of the disease, replenishment of the iron depot, development of complications with side of the cardiovascular system, gastrointestinal tract, secondary immune deficiency, decreased activation of the immune system and disorders with a hundred rons of the cytokine profile. The appointment of pathogenetic treatment led already in the early stages to a significant improvement in the parameters of the studied cytokines, humoral, cellular immunity and nonspecific resistance, iron metabolism, blood tests and general condition against the background of supportive treatment and dynamic observation. The results of clinical and laboratory monitoring of patients showed the high efficiency of the adequate and long-term administration of the drug Sorbifer-Durules in the pathogenetic treatment of not only IDA, but also of developing violations of the level of production of anti-inflammatory cytokines and indicators of immune system activation markers, which did not require the use of additional drugs.

Thus, the foregoing indicates the corrective effect of Sorbifer Durules on indicators of markers of activation of cells of the immune system and the level of production of key cytokines, which also have a regulatory effect on hematopoiesis in patients with chronic IDA.

Table 1 The level of production of cytokines in the blood serum of patients with iron deficiency anemia and in the dynamics of treatment with their drug Sorbifer Durules Indicators Study groups Control n = 40 Patients before treatment n = 40 Patients after treatment n = 31 IL_1 449.95 ± 18.64 632.95 ± 31.21 ^*** 468.13 ± 24.09 ^### IL_6 265.00 ± 18.81 409.18 ± 19.34 ^*** 302.68 ± 22.13 ^### IL_8 1188.93 ± 48.56 1176.79 ± 67.43 871.23 ± 34.10 ^### FNO-α 291.50 ± 10.38 403.05 ± 19.75 ^*** 352.03 ± 22.61 ^# INF-α 51.69 ± 2.98 27.78 ± 1.71 ^*** 41.59 ± 3.00 ^### INF-γ 130.26 ± 7.66 144.19 ± 7.36 111.38 ± 6.08 ^### Note: the statistical significance of the differences with the data of the control group is indicated: * - p <0.05; ** - p <0.01; *** - p <0.001; before and after treatment is indicated: ^# - p <0.05;^## - p <0.01;^### - p <0.001.

table 2 Indicators of markers of activation of the cells of the immune system in patients with iron deficiency anemia and in the dynamics of treatment with their drug Sorbifer Durules Indicators Study groups Control n = 30 Patients n = 102 After treatment, n = 60 CD25 - abs. 0.49 ± 0.05 0.32 ± 0.03 ^** 0.48 ± 0.03 CD25 -% 8.48 ± 0.44 7.06 ± 0.37 ^* 7.74 ± 0.58 CD71 - abs. 0.12 ± 0.01 0.07 ± 0.006 ^* 0.14 ± 0.02 CD71 -% 2.28 ± 0.22 1.85 ± 0.09 ^* 2.21 ± 0.18 CD34 - abs. 0.04 ± 0.001 0.05 ± 0.004 ^** 0.05 ± 0.01 CD34 -% 0.93 ± 0.14 1.22 ± 0.07 ^* 1.13 ± 0.24 Note: the statistical significance of the differences with the data of the control group is indicated: * - p <0.05; ** - p <0.01; *** - p <0.001;
before and after treatment is indicated: ^# - p <0.05;^## - p <0.01;^### - p <0.001.

Claims (1)

The use of Sorbifer Durules as a means for correcting violations of the production of cytokines and indicators of markers of activation of the cells of the immune system in chronic iron deficiency anemia.