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Modern scientific literature contains few reports concerning the influence of target therapy on pathogenetic factors of autoimmune thyroid diseases (AITD). Despite a large number of hypotheses of AITD pathogenesis, the only well established fact is the starting stage of Graves disease (GD) and autoimmune thyroiditis (AIT) is the loss of tolerance to thyroid autoantigens and the final stage is production of autoantibodies to them. Up to 75-80% of the patients with GD have antibodies against thyroid peroxidase and only few of them have anti-thyroglobulin antibodies more characteristic of AIT. Thyrotropin releasing hormone (TRH) is known to stimulate T-lymphocyte production via local effect on insulin-like growth factor (IGF). Modern studies confirm the important role of cytokines in immunopathogenesis of GD and AIT. Moreover, excess activation of this system in AITD provides a basis for the development of specific therapeutic approaches to personified pharmacotherapy. The effectiveness of anti-cytokine therapy of GD and AIT was demonstrated in animal experiments. Studies of therapy targeted on orbital and thyroid autoantigens in AITD are currently underway. The existence of specific receptors and the ability of immunocompetent cells to produce neuropeptides create prerequisites for their participation in intercellular cooperative processes. It can be supposed, by analogy with the influence of hormones and neuromediators on immunocytes, that neurohormones act on them via specific receptors with the involvement of cyclic nucleotides. It opens up opportunity for targeted correction of these relationships. Further studies of immunopathogenetic mechanisms of GD and AIT for better understanding the role of interaction between inborn and acquired immunity, its regulation, and intersystem transmission of signals in the development of these diseases are needed to realize modern strategies of their target therapy.
Modern scientific literature contains few reports concerning the influence of target therapy on pathogenetic factors of autoimmune thyroid diseases (AITD). Despite a large number of hypotheses of AITD pathogenesis, the only well established fact is the starting stage of Graves disease (GD) and autoimmune thyroiditis (AIT) is the loss of tolerance to thyroid autoantigens and the final stage is production of autoantibodies to them. Up to 75-80% of the patients with GD have antibodies against thyroid peroxidase and only few of them have anti-thyroglobulin antibodies more characteristic of AIT. Thyrotropin releasing hormone (TRH) is known to stimulate T-lymphocyte production via local effect on insulin-like growth factor (IGF). Modern studies confirm the important role of cytokines in immunopathogenesis of GD and AIT. Moreover, excess activation of this system in AITD provides a basis for the development of specific therapeutic approaches to personified pharmacotherapy. The effectiveness of anti-cytokine therapy of GD and AIT was demonstrated in animal experiments. Studies of therapy targeted on orbital and thyroid autoantigens in AITD are currently underway. The existence of specific receptors and the ability of immunocompetent cells to produce neuropeptides create prerequisites for their participation in intercellular cooperative processes. It can be supposed, by analogy with the influence of hormones and neuromediators on immunocytes, that neurohormones act on them via specific receptors with the involvement of cyclic nucleotides. It opens up opportunity for targeted correction of these relationships. Further studies of immunopathogenetic mechanisms of GD and AIT for better understanding the role of interaction between inborn and acquired immunity, its regulation, and intersystem transmission of signals in the development of these diseases are needed to realize modern strategies of their target therapy.
One of the factors affecting the prevalence of thyroid disease is the immunopathological process, in particular immunosuppression. The purpose of the study is to determine the characteristics of thyroid gland morphological structure and organometric parameters under immunosuppressive (methotrexate) and immunomodulatory (imunofan) drugs, and immunomodulatory management of immunosuppressive state during early follow-up period (1st and 7th days). Materials and Methods. The study was carried out on 48 white outbred young male rats of the reproductive period, which were divided into 4 groups. The dynamics of structural and organometric parameters of the thyroid gland was studied during the early stages of observation (1st and 7th day) after administration of immunosuppressive (methotrexate) and immunomodulating (imunofan) drugs. Results. When studying microscopic sections of the thyroid gland in animals exposed to methotrexate (group I), imunofan (group II), and after immunomodulatory management of immunosuppressive state (group III), the dynamics in the structure of the thyroid gland was observed during the whole follow-up period. Experimental animals demonstrated insignificant changes in follicles and thyrocytes on the 1st day after the drug administration when compared with those of the control group. The authors didn’t observe any statistically significant deviations in the dynamics of the organometric indicators. Significant deviations were seen on the 7th day of observation. Changes in the morphostructure were revealed after administration of methotrexate (group I): organ mass and volume as well as lobe linear dimensions decreased, indicating an active response of the organ and its depression, which was associated with the drug inhibitory effect on the synthesis, DNA repair and cell mitosis. After isolated administration of an immunomodulator (group II) and in case of immunosuppresson management with imunofan (group III) changes in thyroid morphostructure and organometric parameters were revealed on the 1st and 7th days of observation. Such changes indicated a favorable effect of imunofan on the organ morphofunctional state: organ mass and volume as well as lobe linear dimensions increased. Conclusion. In the early stages of methotrexate administration, the dynamics of thyroid changes indicated the organ depression. Positive dynamics in the thyroid structure was detected after administration of the immunomodulator, however, it was not clear-cut. Keywords: thyroid gland, methotrexate, imunofan, immunosuppression, immunomodulation, correction, organometry.
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