THE ROLE OF HOMOCYSTEINE AS A BIOMARKER OF CYTOKINE STORM IN IMMUNOONCOLOGY AND THERAPY OF COVID-19

Аннотация

INTRODUCTION significant attention as a potential biomarker for Modern medicine faces a number of complex inflammatory processes, including cytokine challenges related to the diagnosis and treatment storms. Elevated homocysteine levels are of diseases characterized by pronounced associated with various pathological conditions, inflammatory reactions and immune system such as cardiovascular diseases, dysfunctions. One such pathological condition is neurodegenerative disorders, and immune the cytokine storm, observed in severe forms of dysfunctions, making it a promising target for COVID-19 and various oncological diseases. A study in the context of new therapeutic cytokine storm represents an excessive activation approaches. of the immune system, leading to the release of large quantities of pro-inflammatory cytokines, The relevance of this topic is driven by the need to which causes systemic inflammation, tissue and identify and develop new biomarkers that could organ damage, and can potentially result in death. not only signal the onset of inflammatory processes but also serve as precise therapeutic In recent years, homocysteine, an amino acid targets for intervention. In the context of the involved in methionine metabolism, has garnered COVID-19 pandemic and the rising incidence of https://www.theamericanjournals.com/index.php/tajmspr 11 THE USA JOURNALS THE AMERICAN JOURNAL OF MEDICAL SCIENCES AND PHARMACEUTICAL RESEARCH (ISSN – 2689-1026) VOLUME 06 ISSUE11 oncological diseases, it is crucial to have a deeper condition characterized by the excessive release of understanding of the pathogenic mechanisms of pro-inflammatory cytokines, leading to systemic these conditions and their relationship with inflammation and multiple organ failure. Recent homocysteine. developments over the last 5-10 years have clearly linked this condition with two major contexts The aim of this study is to investigate the role of (among others): immuno-oncology and, more homocysteine as a biomarker of cytokine storms, recently, COVID-19. Ongoing research focuses on its impact on the pathogenesis of immuno- identifying potential biomarkers that can reliably oncological diseases and COVID-19, and to assess predict both the onset and progression of cytokine the prospects for using homocysteine in the storms, using advanced molecular profiling diagnosis and therapy of these conditions. techniques and large-scale clinical studies. The 1. Mechanisms of Cytokine Storm Onset and Its mechanisms of cytokine storm development are Role in Disease Pathogenesis illustrated below in Figure 1. A cytokine storm is an acute immunopathological Tissue and organ damage Mechanisms Coagulopathy of cytokine Dysregulation and vasculopathy storm development Initiating an immune response Fig.1. Mechanisms of cytokine storm development [1]. https://www.theamericanjournals.com/index.php/tajmspr 12 THE USA JOURNALS THE AMERICAN JOURNAL OF MEDICAL SCIENCES AND PHARMACEUTICAL RESEARCH (ISSN – 2689-1026) VOLUME 06 ISSUE11 elevated levels of AT II, which correlate with the The renin-angiotensin-aldosterone system (RAAS) severity of lung damage. Moreover, the use of ACE is a complex network of vasoactive peptides that inhibitors and angiotensin receptor blockers for play a crucial role in regulating blood pressure, treating arterial hypertension is associated with a circulating blood volume, and electrolyte balance, milder disease course and lower IL-6 levels in as well as participating in inflammatory processes. COVID-19 patients. A meta-analysis involving One of the central components of this system is 24,676 COVID-19 patients confirmed that the use angiotensin-converting enzyme 2 (ACE2), which is of RAAS inhibitors reduces the risk of death and/or expressed in various organs, including the heart, severe conditions by 23% [1]. kidneys, lungs, testes, and gastrointestinal tract. This enzyme catalyzes the conversion of Clinical and epidemiological data suggest that angiotensin I (AT I) into angiotensin 1-9 (AT 1-9), patients with initially reduced ACE2 expression or which can subsequently be transformed into impaired RAAS function (e.g., elderly men, as well angiotensin 1-7 (AT 1-7) under the action of ACE as individuals with diabetes, hypertension, or or other peptidases. Moreover, ACE2 can directly obesity) experience more severe disease when convert angiotensin II (AT II) into AT 1-7. The ACE2 is depleted by the action of SARS-CoV-2 [1]. peptide AT 1-7 possesses vasodilatory, The kallikrein-kinin system also plays an antiproliferative, antithrombotic, and anti- important role in the pathogenesis of COVID-19. inflammatory properties, allowing it to attenuate This system includes kininogen precursors, from the activity of type 1 angiotensin receptors (AT1R). which bradykinin and its active metabolite des- The interaction of AT 1-7 with the Mas receptor Arg9-bradykinin are formed under the action of (MasR) leads to a reduction in the expression of kallikrein. These