On the mechanism of development of autoimmune diseases following exposure to inactivated Mycobacterium tuberculosis

Introduction: High resistance of M. tuberculosis to external conditions, presence of animate reservoirs, adverse socio-economic factors, and inadequate hygiene practices contribute to high incidence of tuberculosis in the world. Effective disease prevention shall be based on scientific substantiation of causality and the mechanisms of its development.

Objective: The study aimed to investigate the etiopathogenesis of autoimmune disorders associated with the exposure of warm-blooded animals to heat killed M. tuberculosis.

Materials and methods: We determined hematological parameters of old Wistar rats using standard methods and estimated the activity of lactate and succinate dehydrogenases (LDH, SDH) in lymphocytes (mitochondria) using a cytobiochemical  method. The clinical and laboratory results were confirmed by X-ray tests.

Results: Inflammation induced by administration of heat inactivated M. tuberculosis (complete Freund’s adjuvant (CFA))  reached the maximum during the third week: the number of white blood cells increased from (9.8 to 11.3) × 109/L compared  to the control animals, normalizing by the seventh week. By the end of the first week, there was a pronounced immune response manifested by the increased erythrocyte sedimentation rate, which later exceeded the threshold limit by 87–100 %.  The autoimmune disease progression was accompanied by impaired cellular respiration (glycolysis and oxidative phosphorylation) by 40 % and 77 %, respectively (p < 0.01). X-ray revealed disorders in the articular apparatus of the exposed animals  including signs of rheumatoid arthritis and bone resorption.

Conclusion: The mechanism of immunotoxicity of M. tuberculosis is associated with impaired energy supply of immune cells and changes in their morpho-functional properties. Based on our findings, we recommend inclusion of drugs with immunomodulatory, antihypoxic and osteoprotective mechanisms in treatment and prevention regimens for tuberculosis and associated diseases to enhance therapeutic efficacy.

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