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Recent Developments in Therapies and Strategies Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Misbah Hameed, M. Zia-Ul-Haq, Marius Moga
Tocilizumab is a monoclonal whole antibody that has been designed to counter the interleukin-6 receptor (IL-6R), which is one of the cytokine linked with the development of some autoimmune diseases. Different cells like B-cells and T-cells, monocytes, fibroblasts, and lymphocytes produce IL-6. IL-6 is also associated with T-cell activation, initiation of protein synthesis in hepatic acute-phase and the instigation of immunoglobulin secretion. Tocilizumab is used in case serious cytokine release syndrome. FDA has permitted phase II clinical trials to evaluate the efficacy of tocilizumab in pneumonia associated with COVID-19 in hospitals. The practice of tocilizumab in patients having severe COVID-19 in China showed positive outcomes to control lung inflammation. Thus “seventh edition of the Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment” included tocilizumab as an option to be used in critical COVID-19 patients showing prevalent lung lesions and higher IL-6 levels [42]. However, some serious side effects associated with the drug has also been observed, such as drug-induced liver injuries and acute liver failure. It can also result in concomitant opportunistic serious infections like Tuberculosis, specially when used in combination with immunosuppressants or corticosteroids.
Interleukin-6 and the Lung
Published in Jason Kelley, Cytokines of the Lung, 2022
Ralph J. Zitnik, Jack A. Elias
Interleukin-6 appears to play an important role in a wide variety of infectious, inflammatory, and neoplastic conditions. IL-6 is involved in these diseases through three major mechanisms. First, IL-6 may act as a systemic hormonelike molecule, signaling injury or stress elsewhere in the body, and marshaling the acute-phase response, which serves to limit tissue injury. Second, uncontrolled production of IL-6 may cause disease by the exaggeration of its normal immune, hematological, and endocrine effects. Finally, IL-6 through its ability to act in an autocrine or paracrine manner can feed back in a positive fashion to perpetuate or amplify inflammatory events and cell proliferative responses. Table 2 lists these three pathogenic mechanisms and the large number of diseases in which each has been implicated.
Conventional Pharmacological Strategies, Investigational Drugs, and Immunotherapies for COVID–19
Published in Srijan Goswami, Chiranjeeb Dey, COVID-19 and SARS-CoV-2, 2022
Subhra Bhattacharya, Srijan Goswami, Chiranjeeb Dey
Tocilizumab is a humanized monoclonal antibody targeted toward the interleukin-6 receptor (IL-6R) intended to inhibit interleukin-6 activity. It is an immunosuppressive drug approved for addressing conditions like cytokine release syndrome (CRS). The data obtained from ongoing clinical trials are not sufficient enough to make any conclusion about the effectiveness of tocilizumab in the management of COVID-19 cases. The documented adverse reactions include infusion reactions, perforations in the gastrointestinal tract, increased neutrophil levels, decreased platelet count, neutropenia, urinary tract infections, liver complications, painful blistering and rashes on the skin, inflammation of the upper respiratory tract, and stools with blood. Clinical trials for the safety and effectiveness of tocilizumab for COVID-19 are in progress. Figure 9.5 represents the concise mechanism of action of Tocilizumab (Office of the Commissioner, 2021b; Actemra® (Tocilizumab) EUA | Patient, n.d.; Ramiro, 2020; AIFA, 2020).
Interleukin-6 in exhaustive exercises and its correlation to bacteremia: a pilot study
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Amr A. Elgharib, Dalia S. Khalifa, Salma A. Khodeer, Youstina Mohsen, Doaa T. Masallat
Cytokines are signaling low molecular weight proteins produced by a broad range of cells as immune cells, endothelial cells, fibroblasts and various stromal cells to regulate the immunity, inflammation and hematopoiesis [1]. They can be classified into family groups according to the types of secondary and tertiary structure or according to cells that secrete them [2]. Interleukin- 6 (IL-6) is an immunomodulatory cytokine with many physiological actions. It is believed that physical exercises induce spikes of the pro-inflammatory and anti-inflammatory cytokines. Regular moderate physical exercises are required to maintain overall balanced health and psychological status, on the other hand, exhaustive exercise was linked to transient immune-suppression which may be due to the elevated levels of cortisol or inhibitory cytokines after strenuous exercises [3]. In addition, cellular immunity is suggested to be suppressed in response to strenuous exercises [4]. Blood samples isolated from individuals participating in extreme endurance events showed that there was transient bacteremia after the event as reported by S. Gill et al [5]. Epidemiological studies show an association between intensity of physical exercise and severity of the body response to infections [6].
Advancements in the pharmacological management of sepsis in the elderly
Published in Expert Opinion on Pharmacotherapy, 2023
Christos Psarrakis, Evangelos J. Giamarellos-Bourboulis
Interleukin-6 (IL-6) is a cytokine produced by a variety of cells, most notably activated macrophages, and mediates the inflammatory response. It is hypothesized that increased levels of IL-6 may assist early diagnosis of sepsis. However, a recent review of 21 studies found limited sensitivity of 66% and specificity of 74% for early sepsis diagnosis. Most studies included in this review had considerable heterogeneity [13]. Main reasons of heterogeneity were the lack of specific cutoffs of diagnosis, the large age variability since seven studies included only patients aged less than 65 years, and the lack of information on the origin of infection. In contrast, another single-center prospective controlled study with 51 septic patients, 46 patients with septic shock and 45 control patients (mean age 75 years) reported that the diagnostic performance of IL-6 was better than any other measured biomarker. At a cutoff value of 52.60 pg/ml, IL-6 could discriminate sepsis patients from controls with 80.4% sensitivity and 88.9% specificity [Area under the curve (AUC): 0.83–0.94, P < 0.001]. At the cutoff of 348.92 pg/ml IL-6 could discriminate patients with septic shock from patients without shock with 76.1% sensitivity and 78.4% specificity [Area under the curve (AUC): 0.71–0.89, P < 0.001]. The diagnostic performance of IL-6 was reported to be better than PCT (AUC: 0.73–0.87, p < 0.001 for sepsis and AUC:0.63–0.83, p < 0.001 for septic shock) [14].
Drugs repurposing for SARS-CoV-2: new insight of COVID-19 druggability
Published in Expert Review of Anti-infective Therapy, 2022
Sujit Kumar Debnath, Monalisha Debnath, Rohit Srivastava, Abdelwahab Omri
Evidence demonstrated interleukin-6 as a prognosticator in COVID-19 patients. This pro-inflammatory cytokine involves the pathogenesis of lung damage leading to SARS-CoV-2 [52]. In this regard, azithromycin effectively reduced the levels of pro-inflammatory cytokines, especially IL-6 [44]. Tocilizumab is an anti-interleukin-6 receptor recombinant monoclonal antibody that shows effectiveness in COVID-19 by lowering CRP and the fatal progression of the disease in hospitalized patients [53]. Targeting NF-κB repressor to induce the production of IL-6 and IL-8 by SARS-CoV-2 nsp-9 and nsp-10 has been confirmed by the peripheral blood mononuclear cell analysis [51]. Glucocorticoids (an inhibitor of NF-κB signaling) downregulates the production of IL-1β, IL-8, IL-6, IL-2, and tumor necrosis factor-α (TNF-α). Due to these activities, glucocorticoids are employed in the ICU patients of COVID-19.