ABSTRACT
The IL-1 family: Members of the IL-1 family of cytokines are similar in structure and function. The functions include agonistic (pro-inflammatory) and antagonistic (anti-inflammatory) activities. The IL-1 family of cytokines can signal damage of tissue integrity, distress, and danger to the organism, ultimately alarming innate and adaptive immunity to fight pathogens. TNF and LT: TNF and LT are trimeric proteins belonging to a structurally related TNF superfamily of cytokines. They are pleiotropic cytokines capable of signaling an array of pro- and anti-inflammatory activities. TNF-α has soluble (sTNF) and membrane (mTNF) forms. Both forms can bind to two TNF receptors (TNF-R1 and TNF-R2), but mTNF can alter the structure of the TNF-R2 such that it binds to sTNF with a lower affinity. Thus, sTNF primarily binds to TNF-R1 and plays an important role in the inflammatory immune response, whereas mTNF-α interacts preferentially with TNF-R2 and promotes cellular proliferation and survival and some other biological effects. IL-6: The IL-6 family of cytokines is structurally characterized by four α-helical bundle structure that signals via the JAK-STAT pathway. IL-6 has a major role in innate and adaptive immunity. IL-6 classic signaling is implicated in acute-phase responses, whereas IL-6 trans-signaling (and trans-presentation/cluster-signaling) characteristically initiates pro-inflammatory pathways with a major impact on adaptive immunity, including plasma cell development and antibody production, and T-cell helper 17 response. Interferons: Interferons are classified into three types. Type I (IFN-α, −β) and type III (IFN-λ) are strong antivirals that can stimulate both innate and adaptive immune responses. Type II interferon (IFN-γ) has a weak antiviral ability, as its major role is in regulating adaptive immunity, particularly in Th1 responses. Cytokine storm and COVID-19: Cytokine storm is a hyperinflammatory state due to overactivity of major pro-inflammatory cytokines like IL-1, IL-6, and TNF. It is a major obstacle for the treatment of severe COVID-19. IL-6 is a potential biomarker for the severity of the disease. Anti-IL-6R (tocilizumab) and anti-virotic "remdesivir” are promising treatments of severe disease. Prevention measures are in place with many auspicious novel vaccines. © 2022 Elsevier Inc. All rights reserved.
ABSTRACT
We could say that sudden death of dr Zoltan Nagy from COVID-19 on Dec 8, 2020 (in his 80th year) marks the end of an epoch in immunology. Just a few weeks before he could have gotten a vaccine, and perhaps enjoyed the benefit of the research in which he invested his working zeal and effort, SARS-Cov-2 claimed another victim - an immunologist.