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

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.

2 tbl, 1 ex

 

The invention relates to medicine, namely Hematology, and can be used for the correction of violations of the production of key cytokines and markers of activation of the immune system, developing in chronic iron deficiency anemia (IDA).

It is known that IDA develops secondary immune deficiency in the form of changes in the indices of non-specific immunity, cellular and humoral immunity, a number of cytokines (Chepurnaya A. N. Immunologic abnormalities in iron deficiency anemia /Materials of all-Russian scientific-practical conference "Actual problems of Hematology and blood transfusion, St. Petersburg, 2002. - P.178).

The prototype of the present invention is the use of stimulant α-interferon-curantyl 300 mg 2 times a week for 2 months on a background of iron preparations. Its application is based on the ability of curantyl activate interferon production by leukocytes (Zybina L. Y. Pathogenesis, clinic, diagnostics and treatment of visceral lesions in iron deficiency States. Abstract. dis. d-pa med. Sciences. - Novosibirsk, 2000. - 57 C.). In the process of treatment received only a slight increase in the level of INF-a, although the number of cases of infectious diseases has decreased by half.

There is a method of treatment of chronic iron deficiency anemia iron supplementation, providing the surrounding vicarious action when deficiencies (Iron deficiency anemia / Butler LI//Novamed-AO.-M, 1998.- 37 C.)and secondary immune deficiency, as normalization of T-lymphocytes in continuing In-helper deficit (Analysis of indicators of immunity in patients with IDA / Videorec SV // Medical business. - 2000. - issue 3-4. - 71-75).

However, a comprehensive study of the effect of iron - Sorbifer Durules, in adequate dosages on the level of production of key cytokines (IL-1, IL-6, IL-8, FNO-α INFαINFγ) and markers of activation of the immune system when IDA was not carried out, which does not allow to adequately assess the state of the immune system in the process of therapy.

The technical result is an expansion of the means for correcting the level of production of key cytokines and markers of activation of the immune system in the treatment of patients with IDA. This technical result is achieved by using Sorbifer Durules as proof of these violations in IDA.

For the correction of the level of production of key cytokines and markers of activation of the immune system drug Sorbifer Durules (approved by the pharmacological Committee of the health Ministry 29.09.99, registration number 011414/01 - 1999) administered 1 tablet 2 times a day (daily dose of 200 mg elemental iron) for 3 months and 3 months maintenance treatment 1 tons/day 10 days after the month when the condition is injured the cause of the disease. The studied parameters were studied before and in the dynamics of treatment (3 weeks treatment).

The use of this drug in 102 patients with chronic iron-deficiency anemia (severe - 50 (49.9 percent); moderate - 52 (51.9 percent) allowed for the first month of treatment almost to restore the level of production of the studied cytokines (p>0.05 with respect to control group) (table 1) and markers of activation of the immune system (table 2). Most sensitive to iron deficiency were INFα, FNO-αbecause their performance was recovering more slowly and had a significant correlation with serum iron (r=-0,33 with IL-1, r=0.39 per with FNO-αp>0,05).

Clinical example: Patient Salimgareeva NA, 53 years, is an ethnic Russian, was in the Hematology Department of the RSC 16.02.2002,, no honey. card 201063. Address: Republic of Belarus, Baltachevski borough, village Starobeshevo, Central street 88. Does not work, education incomplete secondary.

Clinical diagnosis of chronic posthemorrhagic iron deficiency anemia severe. The SOP. Dystonia with cardiac syndrome.

Complaints of weakness, dizziness, palpitations, intermittent, dull, pressing pain in region of heart, shortness of breath on mild exertion, dry skin, hair loss, brittle and striated nails, occasionally eating at the corners of the mouth, BJ whom it has a dough, the chalk. The patient considers himself since 1997 (24). Diagnosed from 1979 was not Treated regularly, iron preparations from 2-3 weeks up to 2 months, with long interruptions, said unstable effect from the treatment. Born 4th account the child. Menstruation from the age of 16, regular, heavy with clots, 7-9 days, pregnancies - 6, birth - 3, abortions - 3, lactation, 1,5-2, Bleeding, blood transfusion was not. Currently menopause within 5 years the balance. Of illness notes SARS 2-3 times a year, pneumonia in 2000, angina in 2001

Objectively: the state of moderate severity, pale skin, dry. The nail plate spoonlike, koilonychia. In the mouth - atrophy of the papillae of the tongue, dental caries. Above the light vesicular respiration, heart rate 84 per minute, blood pressure of 120 and 75 mm RT. Art. the Abdomen is soft, moderately painful epigastric, gastroduodenal zone; the liver and spleen are not enlarged, with the urogenital system without deviations from the norm.

The data of laboratory examinations before and after treatment (the indicators are presented in parentheses).

Complete blood count: erythrocytes - 4,4·1012/l (4,7·1012/l), hemoglobin -63 g/l (98 g/l), MCV - 60 (86,3), sit - 20 (22,8), ICSU - 335 (264), leukocyte - 7,6·109/l (3.5·109/l), thrombocy the s - 300000 (268000), neutrophils: band 1 (2), segmented 65 (75), lymphocytes 29 (18), monocytes 4 (4)%, ESR - 2 mm/hour (6 mm/hour).

Biochemical blood test: whole protein - 79 g/l Albumin - 57,5%, Globulins: α1 - 3,6, α2 - 8,0, β - 10,1, γ - 20,6%, Urea - 4.7 mmol/l, creatinine - 0.09 mmol/l, bilirubin and 10.8 Ámol/l, ACT of 0.10 IU/l, ALT of 0.20 u/l, thymol test - 5,9, serum iron - 3.6 Ámol/l (16,6 umol/L.), ferritin and 6.3 ng/ml (8.8 ng/ml)

The immunological: leukocytes - 8,21·109/l (6,1·109/l), lymphocytes - 2,2·109/l (3,07·109/l), lymphocytes - 27% (38), viability - 3% (4%), T-L - 65% (52%), T-L - 1,43·109/l (1,6·109/l), T-active - 13% (11%), In-l - 0,13·109/l (0,18·109/l),-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 of 4.1 (3,8), Compact. - 83(63).

Phenotypic testing: 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, reaction-acidic, protein - negative, lees - cells 0-1-2. HC - 1013. Analysis on Nechiporenko - 500 leukocytes in 1 ml of erythrocytes 250 in 1 ml.

The reaction of yens Gregersen collection and analysis of feces for the presence of worm eggs - negative.

Conclusion fibrogastroskopii: atrop the ical gastritis.

Radiography of the chest: the chest without pathology.

Electrocardiogram: sinus rhythm, heart rate of 81 per minute, marked degenerative changes in the myocardium.

Ultrasound of the abdominal cavity, retroperitoneal space and pelvis: the size of the liver in the normal range, the echo is diffusely heterogeneous, pathological changes in the other organs of the abdomen and pelvis was not detected.

Consultation of the gynecologist: gynecological diseases no. Endocrinologist: endemic goiter 2 tbsp. without compromising function.

Cardiologist: dystonia with tachycardial syndrome.

For the correction of iron deficiency appointed Arbiter Durules 2 tablets, 2 times for 3 months, followed by a reception maintenance doses for 10 days each month to 3 months.

For dynamic monitoring patient condition improved after 1, 3, 6 months hemoglobin level was - 105 - 118 - 126 g/l, serum iron - 18-20-21 Ámol/l, ferritin - 9,8-11-12,6 ng/ml, cases of infectious diseases were noted.

Thus, there is a long-running course of the disease due to chronic uterine blood loss, multiple pregnancies, births, abortions, prolonged lactation, lack of awareness of the patient, and is also inadequately conducted therapy, lack of control over the course of the disease, supplementation of iron depot, the development of complications of the cardiovascular system, gastrointestinal tract, secondary immune deficiency, decreased activation of the immune system and disorders of the cytokine profile. The purpose of pathogenetic treatment led early on to the significant improvement of the studied cytokines, humoral, cell-mediated immunity and nonspecific resistance, iron metabolism, blood tests and General condition on the background of maintenance treatment and dynamic observation. Results clinical and laboratory monitoring of patients showed high efficiency adequate and long-term purpose of the drug Sorbifer-Durules in the pathogenetic treatment not only IDA, but also developing when it breaches the level of production of inflammatory cytokines and markers of activation of the immune system that did not require the use of additional drugs.

Thus, the above indicates corrective action Sorbifer Durules on markers of activation of cells of the immune system and the level of production of key cytokines, exerting regulatory effects on haematopoiesis in patients with chronic IDA.

Table 1
The level of cytokine production in the serum of patients with iron deficiency anemia and in the dynamics of treatment for their drug Sorbifer Durules
IndicatorsThe treatment group
Control n=40Patients before treatment n=40Patients after treatment n=31
IL_1449,95±18,64632,95±31,21***468,13±24,09###
IL_6265,00±18,81409,18±19,34***302,68±22,13###
IL_81188,93±48,561176,79±67,43871,23±34,10###
FNO-α291,50±10,38403,05±19,75***352,03±22,61#
INFα51,69±2,9827,78±1,71***41,59±3,00###
INFγ130,26±7,66144,19±of 7.36111,38±between 6.08###
Note: the statistical significance of the differences with the data of the control group indicated: * p<0,05; ** - p<0,01; *** p<0,001; before and after treatment indicated:#- p<0,05;##- p<0,01;###- p<0,001.

Table 2
Markers of activation of cells of the immune system in patients with iron deficiency anemia and in the dynamics of treatment for their drug Sorbifer Durules
IndicatorsThe treatment group
Control n=30Patients n=102After treatment n=60
CD25 - abs.0,49±0,050,32±0,03**0,48±0,03
CD25 - %8,48±0,447,06±0,37*7,74±0,58
CD71 - abs.0,12±0,010,07±0,006*0,14±0,02
CD71 - %2,28±0,221,85±0,09*2,21±0,18
CD34 - abs.0,04±0,0010,05±0,004**0,05±0,01
CD34 - %0,93±0,141,22±0,07*1,13±0,24
Note: the statistical significance of the differences with the data of the control group indicated: * p<0,05; ** - p<0,01; *** p<0,001;

before and after treatment indicated:#- p<0,05;##- p<0,01;###- p<0,001.

< num="39"> The use of Sorbifer Durules as a means for the correction of violations of the production of cytokines and markers of activation of cells of the immune system in chronic iron deficiency anemia.



 

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