Multiple Sclerosis is a Risk Factor for Hyperthyroidism and Interferon Beta Action on Thyroid Hormones via Novel Immuno-neuro-enzymological Mechanisms

Authors

  • Rasha Zuhair Jasim Department of chemistry/ College of education for pure science Ibn Al Haitham / University of Baghdad

DOI:

https://doi.org/10.32947/ajps.v20i4.777

Abstract

Objective : Multiple  sclerosis (MS) is a common neurological disease deeply linked with the immune-inflammatory disorders whereas the term (multiple) mostly refers to the multi-focal zones of

 

 

Inflammation caused by lymphocytes and macrophages infiltration besides oligodendrocytes death. Accordingly , the dysfunctional immune system able to damage myelin ( a pivotal component of the central nervous system ) which responsible for communication among neurons. The aim of the present study is to innovate a biochemical relationship between MS and thyroid hormones (THs) by highlighting immunological responses and also to examine the action of Interferon beta (IFNβ) drug on thyroid hormone (THs) and thyroid stimulation hormone (TSH). Materials and methods: Sixty (60) Iraqi women in the age ranged (36-43) years were enrolled in the present study, (30) of them were MS patients and the other (30) were healthy. Anyway, the protocol of the study involved four groups: G1 is a healthy control group, G2 involved untreated MS patients, G3 included the MS patients treated with IFNβ for (6) weeks and G4 composed of the same patients treated with IFNβ for (12) weeks. THs (T4 and T3) and TSH levels were determined in sera of all groups.  Results: Data of the present study have reported that T4 level was highly significant increase in sera of G2 compared with G1 while it was significant and highly significant decreased in G3 and G4 respectively compared with G2, the difference between G4 and G1 and also between G4 and G3 was significant. T3 level was highly significant increase in sera of G2 compared with G1 but it was highly significant decreased in G3 and G4 compared with G2, the difference between G4 and G1 was non-significant while the difference between G4 and G3 was significant. Conversely, TSH level was highly significant decreased in G2 compared with G1 but it was highly significant increase in G3 and G4 compared with G2, the difference between G4 and G1 and also between G4 and G3 was highly significant. Conclusions : Interestingly , the present study is the first in Iraq reporting that MS may be a key risk factor for hyperthyroidism and also the first suggesting that IFNβ regulates THs biosynthesis via novel immuno-neuro-enzymological mechanisms regarding thyroid peroxidase (TPO) and iodothyronine deiodinase 1 (D1), meanwhile the present study indicates that  IFNβ has an indirect antioxidant activity. Moreover, the present study provides a definite clarification for the changed NF kappa B level in MS. Remarkably, the present study reveals that IFNβ is more potent on T3 than T4 while it has less action on TSH.

References

- Zaminpira, S. and Niknamin , S.; The main cause and prevention of multiple sclerosis and its relation to cancer . EC Cancer. 2017. Vol. 2.5. Pp: 217-226.

- Leibowitz, S. and Yan, J.; NF-kB pathways in the pathogenesis of Multiple sclerosis and thetherapeutic implications. FRONT MOL NEROSCI. 2016. Vol. 9. Pp: 1- 23. DOI: https://doi.org/10.3389/fnmol.2016.00084

- Kasper, L. and Reader, A.; Immunomodulatory activity of interferon beta. ANN CLIN TRANSL NEUR. 2014. Vol.1. Pp: 622-631. DOI: https://doi.org/10.1002/acn3.84

- Kappos , L. ; Edan , G. ; Freedman , M. and et al.; The 11-years long-term follow-up study from randomized benefit CIS trial. Neurology. 2016. Vol.87. Pp: 978-987. DOI: https://doi.org/10.1212/WNL.0000000000003078

- Nadeem, M.; Sklovers, L. and Sloane, J.; Targrting remyelination treatment for multiple sclerosis. World J neurol. 2015. Vol.5. Pp: 5-16. DOI: https://doi.org/10.5316/wjn.v5.i1.5

- Hanafy, K. and Sloane, J.; Regulation of remyelination in multiplesclerosis. FEBS Journal. 2015. Vol. 585. Pp: 3821-3828. DOI: https://doi.org/10.1016/j.febslet.2011.03.048

- Bernitas, E.; Pathophysiology and imaging diagnosis of demyelinating disorders. Brain Sci. 2018.Vol. 8. Pp:1-3. DOI: https://doi.org/10.3390/brainsci8030044

- Bando, Y.; Mechanism of demyelination and remyelination in multiple sclerosis. Clin Exp Neuroimmunol. 2020.Vol.11. Pp:14-21. DOI: https://doi.org/10.1111/cen3.12576

- Ghasemi, N.; Razavi, S. and Nikzad , E.; Multiple sclerosis pathogenesis , symptoms , diagnosis and cell –based therapy . Cell J. 2017. Vol. 19. Pp:1-10.

- Reich, D.; Luncheonette, C. and Calabresi, P.; Multiple sclerosis. New Eng J Med. 2018. Vol. 378. Pp: 169-180. DOI: https://doi.org/10.1056/NEJMra1401483

- Nakamura, Y.; Gaetano, L.; Matsushita, T. and et al.; A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by race with reference to disability progression. J. neuroin-flammation. 2018. Vol. 15. Pp:1-11. DOI: https://doi.org/10.1186/s12974-018-1295-1

- Muhammad, J.; Mahmood, M. and Admon, A.; Kala azar one of the diseases that play role in autoimmune thyroid diseases. AJPS. 2011. Vol. 10. Pp:123-136. DOI: https://doi.org/10.32947/ajps.v10i2.302

- Leso , V. ; Vetrani , I. ; Sicignano , A. ; Ronano , R. and Iavicoli , I.; The impact of shift- work and night shift – work on thyroid : a systematic review. Int. J. Environ. Res. Public Health. 2020. Vol. 17. Pp:1-17. DOI: https://doi.org/10.3390/ijerph17051527

- Alomar, M.; Vuddanda, P.; Trenfield, S.; Dodoo, C.; Velaga, S.; Basit, A. and Gainsford, S.; Printing T3 and T4 oral drug combinations as a novel strategy for hyperthyroidism. Int J Pharm. 2018. Vol. 549. Pp:363-369. DOI: https://doi.org/10.1016/j.ijpharm.2018.07.062

- Noran, R. and Hedef, E.; Thyroid function tests, lipid profile and the diagnosis of thyroid diseases. AJPS. 2005. Vol.2. Pp:58-62. DOI: https://doi.org/10.32947/ajps.v2i2.434

- Singh, S.; Yazdani, U.; Gadad, B.; Zaman, S. et al.; Serum thyroid stimulation hormone and interleukin-8 levels in boys with autism spectrum disorder. J. Neuroinflammation. 2018. Vol.14. Pp: 1-7. DOI: https://doi.org/10.1186/s12974-017-0888-4

- Priyanka, R. and Muralitharan, M.; Interferons and interferon therapy. JPSR. 2014. Vol. 6. Pp: 400-403.

- Hurtado-Guerrero , I ; Pinto-Medel , M. Urbaneja , P. ; Rodriguez-Bada , J. ; Ortega-Pinazo , M. ; Serrano , P. ; Fernandez , O. ; Leyva , L. and Oliver-Martos , B.; Cross – reactivity of antibodies against interferon beta in multiple sclerosis patients and interference of the JAK-STAT signaling pathway. SCIENTIFIC REPORTS .2017. Vol. 7. Pp:1-10. DOI: https://doi.org/10.1038/s41598-017-16828-x

- Godlewska, M.; Krasuska, W. and Czarnecki, B.; Biochemical properties of thyroid peroxidase (TPO) expressed in human breast and mammary – derived cell lines. PLOS.ONE. 2018. Vol. 13. Pp: 1-14. DOI: https://doi.org/10.1371/journal.pone.0193624

- Raj, K.; Thyroid function tests and its interrelation, J. pathol. of Nepal. 2014. Vol.4. Pp: 584-590. DOI: https://doi.org/10.3126/jpn.v4i7.10318

- Nazar, M.; Nicola, J.; Velez, M.; Pellizas, C. and Masini – Repiso, A.; Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)- kB p65 subunit phosphorylation. Endocrinology. 2012. Vol. 153. Pp: 6114-6125. DOI: https://doi.org/10.1210/en.2012-1567

- Citterio, C.; Veluswamy, B.; Morgans , S. and et al.; De novo triiodothyronine formation from throcytes activated by thyroid stimulating hormone. J. Biol. Chem. 2017. Vol. 292. Pp: 15434-15444. DOI: https://doi.org/10.1074/jbc.M117.784447

- Al- Badri, G. and Castorina , A.; Insights into the role of neuroinflammation in the pathogenesis of multiple sclerosis , J. funct. Morphol. Kineiol. 2018. Vol. 3. Pp: 1-14. DOI: https://doi.org/10.3390/jfmk3010013

- Cao, L. and He, C.; Polarization of macrophages and microglia in inflammatory demyelination. Neurosci. Bull. 2013. Vol. 29. Pp: 189-198. DOI: https://doi.org/10.1007/s12264-013-1324-0

- Ellrichmann, G.; Thone, J.; Lee, D.; Rupec, R.; Gold, R. and Linker, R.; Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation. J. Neuroinflammation. 2012. Vol. 9. Pp: 1-11. DOI: https://doi.org/10.1186/1742-2094-9-15

- Srinivasan, M. and Lahirl, D.; Significance of NF-kB as a potential therapeutic target in the neurodegenerative pathologies of Alzeheimers disease and multiple sclerosis and multiple sclerosis. Expert Opin Ther Targets. 2015. Vol.19. Pp: 471-487. DOI: https://doi.org/10.1517/14728222.2014.989834

- Pires, B.; Silva, R.; Ferreira, G. and Alhany, E.; NF-kappa B: two sides of the same coin. Genes. 2018. Vol. 9. Pp: 1-23. DOI: https://doi.org/10.3390/genes9010024

- Shih, R.; Wang, C. and Yang, C.; NF-kappa B signaling pathways in neurological inflammation: A mimi review. FRONT MOL NEUROSCI. 2015. Vol. 8. Pp:1-8. DOI: https://doi.org/10.3389/fnmol.2015.00077

- Kaltschmidt, B, and Kaltschmidt , C.; NF- kappa B in the nervous system . Cold Spring Harb Prespect Biol. 2009. Vol.1. Pp: 1-13. DOI: https://doi.org/10.1101/cshperspect.a001271

- Levine, S.; The role of reactive oxygen species in the pathogenesis of multiple sclerosis. Med. Hypotheses. 1992. Vol. 39. Pp: 271-274. DOI: https://doi.org/10.1016/0306-9877(92)90121-R

- Mancini, A.; Segni, C.; Raimondo, S.; Olivier, G.; Silvestri in, A.; Meucci, E. and Curro, D.; Thyroid hormones, oxidative stress, and inflammation. MEDIAT INFLAMM. 2016. Vol. 2016. Pp: 1-12. DOI: https://doi.org/10.1155/2016/6757154

- Vaismann, M, Rosenthal, D. and Carvalho, D.; Enzyme involved in thyroid iodide organification. Arq Bras endocrinol and metabol. 2004. Vol. 48. Pp:9-15. DOI: https://doi.org/10.1590/S0004-27302004000100003

- Massart, C.; Hoste, C.; Virion, A.; Ruf , J. ; Dumont , J. and Sande , J.; Cell biology of H2O2 generation in the thyroid : Investigation of the control dual oxidases (DUOX) activity in intact ex vivo thyroid tissue and cell lines. Mol. Cell. Endocrinol. 2011. Vol. 347. Pp:32-44. DOI: https://doi.org/10.1016/j.mce.2011.05.047

- Pertosovkaya, I.; Abad, E.; Puig, N.; Garcia-Ojalvo, J. and Villoslada, P.; Transient oscillatory dynamics of interferon beta signaling in macrophages. BMC Syst Biol. 2013. Vol. 7. Pp: 1-12. DOI: https://doi.org/10.1186/1752-0509-7-59

- Gold, J.; Hoshino, Y.; Hoshino, M.; Nolan, A. and Weiden, M.; Exogenous gamma and alpha / beta interferon rescues human macrophages from cell death induced by bacillus anthracis. INFECT. IMMUN. 2004. Vol. 72. Pp:1291-1297. DOI: https://doi.org/10.1128/IAI.72.3.1291-1297.2004

- Maia, A.; Goemann, L.; Meyer, E. and Wajner, S.; Type 1 iodothyronine deiodinase in human physiology and disease. Endocrinology. 2011. Vol.209. Pp:283-297. DOI: https://doi.org/10.1530/JOE-10-0481

- Galecka, E.; Kumor-/kisielewska, A.; Orzechowska, A.; Maes, M. Gorski, P. and Szemraj, J.; Assessment of type 1 and type 3 deiodinase expression levels in depressive disorders. Acta Neurobiol Exp (Wars). 2017. Vol. 77. Pp: 225-235. DOI: https://doi.org/10.21307/ane-2017-056

- Darras, V. and Herck, S.; Iodothyronine deiodinase structure and function: from ascidians to humans. Endocrinology. 2012. Vol.215. Pp: 189-206. DOI: https://doi.org/10.1530/JOE-12-0204

- Galton, V.; Waard, E.; Parlow, A.; Germain, D. and Hernadez, A.; Life without the iodotyronine deiodinase. Endocrinology. 2014. Vol. 155. Pp: 4081-4087. DOI: https://doi.org/10.1210/en.2014-1184

- Rackov, G.; Shokri, R.; Mon, M.; Martinez-A, C. and Balomenos , D.; The role of IFN –β during the course of sepsis progression and its therapeutic potential . FRONT IMMUNOL. 2017. Vol. 8. Pp: 1-8. DOI: https://doi.org/10.3389/fimmu.2017.00493

- Kopitars-Jerala, N.; The role of interferons in inflammation and inflammasome activation. FRONT IMMUNOL. 2017. Vol. 8. Pp: 1-9. DOI: https://doi.org/10.3389/fimmu.2017.00873

- Tovey, M. and Lallemand, C.; Safety, Tolerability and immunogenicity of interferons. Pharmaceuticals. 2010. Vol. 3. Pp:1162-1186. DOI: https://doi.org/10.3390/ph3041162

- Hoermann, R.; Midgley, J.; Larish , R. and Dietrich , J.; Recent advances in thyoid hormone regulation : Toward a new paradigm for optimal diagnosis and treatment. FRONT IMMUNOL. 2017.Vol. 8. Pp: 1-8. DOI: https://doi.org/10.3389/fendo.2017.00364

- Hoermann, R.; Midgley, J.; Larish, R and Dietrich, J.; The role of functional thyroid capacity in pituitary thyroid feedback regulation. EUR J CLIN INVEST. 2018. Vol. 1. Pp:1-25. DOI: https://doi.org/10.1111/eci.13003

- Mullur, R.; Liu, Y. and Brent, G.; Thyroid hormone regulation of metabolism. Physiology Rev. 2014. Vol. 94. Pp: 355-382. DOI: https://doi.org/10.1152/physrev.00030.2013

- Biswas, K.; Nandi, T.; Sattar, T. and Rahman, A.; Investigatin of thyroid hormone status among obese women on the endocrine outpatient's department in a tertiary level hospital. Pharm Pharmacol Int J. 2017.Vol. 5. Pp: 147-149. DOI: https://doi.org/10.15406/ppij.2017.05.00129

- Kahaly, G.; Bartalena, L.; Hegedus, L. Leenhardt, L.; Poppe, K. and Peare, S.; 2018 European thyroid association guideline for the management of Graves hyperthyroidism. Eur Thyroid J. 2018. Vol.7. Pp: 167-186 DOI: https://doi.org/10.1159/000490384

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Published

2022-04-18

How to Cite

Rasha Zuhair Jasim. (2022). Multiple Sclerosis is a Risk Factor for Hyperthyroidism and Interferon Beta Action on Thyroid Hormones via Novel Immuno-neuro-enzymological Mechanisms. Al Mustansiriyah Journal of Pharmaceutical Sciences, 20(4), 72–81. https://doi.org/10.32947/ajps.v20i4.777