The Important Role of Interleukin-2 in COVID-19

Abstract

There is controversial literature about the effects of the interleukin-2 (IL-2) cytokine family in COVID-19 pathogenesis and immunity. So we aimed to identify the potential in the role of the IL-2 family in COVID-19. A narrative review search was done through online databases, including PubMed, Scopus, and Web of Science. The search deadline was up to December 2022. We applied no time limits for the searching strategy. After retrieving articles from the databases, the authors summarized the data into two data extraction tables. The first data extraction table described the changes in the IL-2 cytokine family in COVID-19 and the second table described the therapeutic interventions targeting IL-2 family cytokines. The results of the literature on the role of the IL-2 cytokine family do not show a singular rule. IL-2 cytokine family can change during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some studies suggest that IL-2 cytokine family rise during the infection and cause severe inflammatory response and cytokine storm. These cytokines are shown to be increased in immunocompromised patients and worsen their prognosis. In individuals without underlying disease, the upregulation of the IL-2 family shows the clinical outcome of the disease and rises with disease severity. However, some other studies show that these cytokines do not significantly change. IL-2 cytokine family is mostly upregulated in healthy individuals who had vaccination, but immunocompromised patients did not show significant changes after a single dose of vaccines, which shows that these patients need booster doses for efficient immunity. IL-2 cytokine family can also be used as immunotherapy agents in COVID-19.

Figure 1

The general mechanism underlying immune system response to SARS-CoV-2 invasion. When the PAMP of the virus attaches to the PRR, the pattern of the virus is detected by immune system. This leads to a signal transduction to the genome of immune cells and as a result, it can activate the cytokine genes. Activation of cytokine genes lead to cytokine release. If the cytokine release happens excessively, the cytokine storm happens.

Figure 2

IL-2 cytokine family changes after SARS-CoV-2 infection.

Figure 3

1: Coronavirus infects lung cells; 2: antigen presenting cells (APCs) attach to T helper and T cytotoxic cells, which in turn produce IL-2 cytokine family cytokines, creating a cycle of inflammation that damages the lung cells; 3–5: lung fibrosis can occur through the formation of fibrin. Blood vessels are filled with fluid leading to respiratory failure and patient poor prognosis.