Biochemical markers of inflammation in drug-resistant tuberculous meningitis (experimental study)

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Abstract

Introduction. The determination of inflammatory markers used to monitor the course of the disease and monitor the effectiveness of treatment.

Goal. To evaluate biochemical markers of inflammation in cerebrospinal fluid (CSF) and blood serum in experimental meningitis caused by a multidrug-resistant strain of M. tuberculosis.

Material and methods. Three groups of rabbits studied: infection control (IC) – infected, untreated; treatment control (TC) – those who received anti-tuberculosis drugs (ATD) in accordance with the spectrum of drug sensitivity; the main group (MG) – infected who received roncoleukin (12.5 mcg/kg, 5 injections, 1 time every 3 days) against the background of ATD. The glucose, total protein, albumin, ceruloplasmin, elastase, adenosine deaminase (ADA), its isoenzymes evaluated in CSF and serum.

Results. After 4 months of treatment, the number of neutrophils in the CSF decreased in the TC and MG, and lymphocytes increased in the TC and a decrease in MG. The total protein level decreased in the MG. There was a tendency to decrease glucose in the MG compared to the TC. ADA decreased in the TC and MG. The serum levels of albumin, ceruloplasmin, glucose, total protein in these groups remained within the baseline values. ADA in the TC increased, while ADA-1 only tended to increase. In the MG, an increase in elastase detected.

Conclusion. A decrease in the activity of the inflammatory process was revealed in both the TC and MG groups, and more significant with the administration of roncoleukin along with ATD. Assessment of the activity of ADA and its isoenzymes in CSF is important in assessing the regression of a specific inflammatory process during the treatment of experimental TBM.

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About the authors

Marina Evgenievna Dyakova

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia

Author for correspondence.
Email: marinadyakova@yandex.ru
ORCID iD: 0000-0002-7810-880X

Senior Researcher, Research Laboratory of Microbiology, Biochemistry and Immunogenetics

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036

Tatyana Ivanovna Vinogradova

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia

Email: vinogradova@spbniif.ru

Head of the Research Laboratory of Experimental Medicine,  Doctor of Medical Sciences, Professor

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036

Boris Mikhailovich Ariel

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia

Email: arielboris@rambler.ru
ORCID iD: 0000-0002-7243-8621

Advisor to the Director, Doctor of Medical Sciences, Professor

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036

Dilyara Salievna Esmedlyayeva

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia

Email: diljara-e@yandex.ru
ORCID iD: 0000-0002-9841-0061

Senior Researcher of the Research Laboratory of Microbiology, Biochemistry and Immunogenetics, Candidate of Biological Sciences

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036

Alexander Mikhailovich Panteleev

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia

Email: alpanteleev@gmail.com
ORCID iD: 0000-0002-8307-7622

Leading Researcher of the Research Group of Epidemiology and Intellectual Monitoring, Doctor of Medical Sciences

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036

Natalia Mikhailovna Blum

FSBMEI HE “Military Medical Academy named after S.M. Kirov” of the Ministry of Defense of the Russian Federation

Email: blumn@mail.ru
ORCID iD: 0000-0003-1445-6714

Senior Lecturer at the Department of Pathological Anatomy

Russian Federation, Akademika Lebedeva str., 6J, Saint-Petersburg, 194044

Elena Radievna Mukhametshina

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia

Email: doctor.mukhametshinaer@gmail.com
ORCID iD: 0000-0003-3312-0829

Radiologist, Magnetic Resonance Imaging laboratory

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036

Marine Zaurievna Dogonadze

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia

Email: marine-md@mail.ru

Senior Researcher of the Research Laboratory of Microbiology, Biochemistry and Immunogenetics

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036

Alexander Sergeevich Kurdoyak

Saint Petersburg State Budgetary Healthcare Institution “City Anti-Tuberculosis Dispensary”

Email: kurdoyak_a_s@mail.ru

Head of department No.3

Russian Federation, Zvezdnaya St., 12, Saint-Petersburg, 196142

Natalya Vyacheslavovna Zabolotnyk

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia

Email: zabol-natal@yandex.ru
ORCID iD: 0000-0002-9186-6461

Leading Researcher of the Research Laboratory of Experimental Medicine

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036

Anastasia Igorevna Lavrova

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia

Email: aurebours@googlemail.com
ORCID iD: 0000-0002-8969-535X

Leading Researcher at the Scientific and Clinical Center for Spinal Surgery

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036

Arkady Anatolyevich Vishnevskiy

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia

Email: aa.vichnevsky@spbniif.ru

Leading Researcher at the Scientific and Clinical Center of Pathology

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036

Petr Kazimirovich Yablonskiy

FSBEI HE “Saint-Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of Russia; Saint-Petersburg State University

Email: piotr_yablonskii@mail.ru
ORCID iD: 0000-0003-4385-9643

Director, Head of Hospital Surgery Department, Faculty of Medicine, Doctor of Medical Sciences, Professor

Russian Federation, Ligovsky ave., 2–4, Saint-Petersburg, 191036; Universitetskaya nab. 7/9, Saint-Petersburg, 199034

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2. Fig. 1. MR images of the rabbit brain in sagittal and axial projections: а – healthy (uninfected rabbit) – signs of signal amplification along the membranes and in the brain are not detected; б and в – MR-signs of menigoencephalomyelitis in infected (untreated) animals: б and в – signal amplification along the membranes of stem structures along the anterior and left lateral surfaces of the medulla oblongata and spinal cord; в – signs of nodular contrast in the right lateral cords of the medulla oblongata and spinal cord, 4×5 in size 5×6 mm with clear contours

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3. Fig. 2. Dynamics of ADA, ADA-2, and elastase activity in different groups of rabbits: a) infection control – solid line (circle), б) treatment control – dashed line (square) в) the main group is dotted (rhombus)

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4. Fig. 3. a – is the brain of a rabbit from the IC group. Epithelioid cell granulomas with giant multinucleated Langhans type cells; staining of preparations with hematoxylin and eosin, ×200; б, в – the brain of rabbits from the TC and MG groups, respectively. Epithelioid cell granulomas without giant Langhans cells, with central micronecrosis; staining of preparations with hematoxylin and eosin, ×100

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5. Fig. 4. a, б, в – the brain of rabbits of groups IC, MG and TC, respectively. Scanty perivascular infiltrates consisting mainly of lymphocytes and microglial cells in the IC group, pronounced lymphoplasmocytic capillary infiltration in the MG group, clutch-like infiltrates consisting of epithelioid cells and lymphocytes in the TC group Note. Staining of preparations with hematoxylin and eosin, ×200.

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