Journal of Population Therapeutics & Clinical Pharmacology

The SARS-CoV-2 virus causes a contagious disease known as Coronavirus Disease 2019 (COVID-19). It began spreading globally in 2019 and is still producing pandemics today. Different COVID-19 vaccinations offer protection against this illness. Pfizer-BioNTech and Sinopharm were the two vaccine manufacturers with the highest usage in Iraq. Both vaccines use a different method to activate the immune system. This study seeks to compare the IL-22, IL-37, and IL-38 levels in those who received either the Sinopharm or the Pfizer-BioNTech COVID-19 vaccination. IL-22, IL-37, IL-38 levels have been shown to be upregulated in COVID-19 patients. In this study, IL-22, IL-37, and IL -38 levels were tested in 80 healthy controls and 100 COVID-19 patients 14-21 days after recovery. Additionally, people who received the Sinopharm or Pfizer-BioNTech vaccine (50 each) were monitored 21 days after the first dosage and 21 days after the second dose. In comparison to controls, serum levels were noticeably higher in recovered patients. Except for the first dosage of Pfizer BioNTech, the first and second doses of Sinopharm and Pfizer BioNTech were linked to considerably higher levels of IL-22, IL-37, and IL-38 compared to controls or recovered patients. where IL-22, IL -37, and IL-38 levels did not show significant differences compared to recovered patients. In conclusion, lower IL-37 and IL-38 molecule levels were linked to recovery from COVID-19, although these levels remained considerably greater in recovered patients compared to uninfected controls. Vaccination with Sinopharm or Pfizer-BioNTech confirmed the up-regulating effects of SARS-CoV-2 on IL-22, IL-37, and IL-38 levels.

Clinical relevance and therapeutic potential of IL-38 in immune and non-immune-related disorders

Interleukin-38 (IL-38) is the most recent member of the IL-1 family that acts as a natural inflammatory inhibitor by binding to cognate receptors, particularly the IL-36 receptor. In vitro, animal and human studies on autoimmune, metabolic, cardiovascular and allergic diseases, as well sepsis and respiratory viral infections, have shown that IL-38 exerts an anti-inflammatory activity by modulating the generation and function of inflammatory cytokines (e.g. IL-6, IL-8, IL-17 and IL-36) and regulating dendritic cells, M2 macrophages and regulatory T cells (Tregs). Accordingly, IL-38 may possess therapeutic potential for these types of diseases. IL-38 down-regulates CCR3+ eosinophil cells, CRTH2+ Th2 cells, Th17 cells, and innate lymphoid type 2 cells (ILC2), but up-regulates Tregs, and this has influenced the design of immunotherapeutic strategies based on regulatory cells/cytokines for allergic asthma in future studies. In auto-inflammatory diseases, IL-38 alleviates skin inflammation by regulating γδ T cells and limiting the production of IL-17. Due to its ability to suppress IL-1ß, IL-6 and IL-36, this cytokine could reduce COVID-19 severity, and might be employed as a therapeutic tool. IL-38 may also influence host immunity and/or the components of the cancer microenvironment, and has been shown to improve the outcome of colorectal cancer, and may participate in tumour progression in lung cancer possibly by modulating CD8 tumour infiltrating T cells and PD-L1 expression. In this review, we first briefly present the biological and immunological functions of IL-38, and then discuss the important roles of IL-38 in various types of diseases, and finally highlight its use in therapeutic strategies.

The abundance of Interleukin-22, 37, and 38 post-vaccination and following COVID-19 recuperation

The SARS-CoV-2 virus causes a contagious disease known as Coronavirus Disease 2019 (COVID-19). It began spreading globally in 2019 and is still producing pandemics today. Different COVID-19 vaccinations offer protection against this illness. Pfizer-BioNTech and Sinopharm were the two vaccine manufacturers with the highest usage in Iraq. Both vaccines use a different method to activate the immune system. This study seeks to compare the IL-22, IL-37, and IL-38 levels in those who received either the Sinopharm or the Pfizer-BioNTech COVID-19 vaccination. IL-22, IL-37, IL-38 levels have been shown to be upregulated in COVID-19 patients. In this study, IL-22, IL-37, and IL-38 levels were tested in 80 healthy controls and 100 COVID-19 patients 14-21 days after recovery. Additionally, people who received the Sinopharm or Pfizer-BioNTech vaccine (50 each) were monitored 21 days after the first dosage and 21 days after the second dose. In comparison to controls, serum levels were noticeably higher in recovered patients. Except for the first dosage of Pfizer BioNTech, the first and second doses of Sinopharm and Pfizer BioNTech were linked to considerably higher levels of IL-22, IL-37, and IL-38 compared to controls or recovered patients. where IL-22, IL-37, and IL-38 levels did not show significant differences compared to recovered patients. In conclusion, lower IL-37 and IL-38 molecule levels were linked to recovery from COVID-19, although these levels remained considerably greater in recovered patients compared to uninfected controls. Vaccination with Sinopharm or Pfizer-BioNTech confirmed the up-regulating effects of SARS-CoV-2 on IL-22, IL-37, and IL-38 levels.Copyright © 2023, Codon Publications. All rights reserved.

Difference in mortality rates in hospitalized COVID-19 patients identified by cytokine profile clustering using a machine learning approach: An outcome prediction alternative.

COVID-19 is a disease caused by the novel Coronavirus SARS-CoV-2 causing an acute respiratory disease that can eventually lead to severe acute respiratory syndrome (SARS). An exacerbated inflammatory response is characteristic of SARS-CoV-2 infection, which leads to a cytokine release syndrome also known as cytokine storm associated with the severity of the disease. Considering the importance of this event in the immunopathology of COVID-19, this study analyses cytokine levels of hospitalized patients to identify cytokine profiles associated with severity and mortality. Using a machine learning approach, 3 clusters of COVID-19 hospitalized patients were created based on their cytokine profile. Significant differences in the mortality rate were found among the clusters, associated to different CXCL10/IL-38 ratio. The balance of a CXCL10 induced inflammation with an appropriate immune regulation mediated by the anti-inflammatory cytokine IL-38 appears to generate the adequate immune context to overrule SARS-CoV-2 infection without creating a harmful inflammatory reaction. This study supports the concept that analyzing a single cytokine is insufficient to determine the outcome of a complex disease such as COVID-19, and different strategies incorporating bioinformatic analyses considering a broader immune profile represent a more robust alternative to predict the outcome of hospitalized patients with SARS-CoV-2 infection.

Calprotectin and Imbalances between Acute-Phase Mediators Are Associated with Critical Illness in COVID-19.

The trajectory from moderate and severe COVID-19 into acute respiratory distress syndrome (ARDS) necessitating mechanical ventilation (MV) is a field of active research. We determined serum levels within 24 h of presentation of 20 different sets of mediators (calprotectin, pro- and anti-inflammatory cytokines, interferons) of patients with COVID-19 at different stages of severity (asymptomatic, moderate, severe and ARDS/MV). The primary endpoint was to define associations with critical illness, and the secondary endpoint was to identify the pathways associated with mortality. Results were validated in serial measurements of mediators among participants of the SAVE-MORE trial. Levels of the proinflammatory interleukin (IL)-8, IL-18, matrix metalloproteinase-9, platelet-derived growth factor (PDGF)-B and calprotectin (S100A8/A9) were significantly higher in patients with ARDS and MV. Levels of the anti-inflammatory IL-1ra and IL-33r were also increased; IL-38 was increased only in asymptomatic patients but significantly decreased in the more severe cases. Multivariate ordinal regression showed that pathways of IL-6, IL-33 and calprotectin were associated with significant probability for worse outcome. Calprotectin was serially increased from baseline among patients who progressed to ARDS and MV. Further research is needed to decipher the significance of these findings compared to other acute-phase reactants, such as C-reactive protein (CRP) or ferritin, for the prognosis and development of effective treatments.