tetano
Editor, Senior Moderator
J Cell Physiol
. 2020 Aug 13.
doi: 10.1002/jcp.30008. Online ahead of print.
IL-18 and infections: Is there a role for targeted therapies?
Alessandra Vecchi?[SUP] 1 [/SUP], Aldo Bonaventura[SUP] 1 2 [/SUP], Stefano Toldo[SUP] 1 [/SUP], Lorenzo Dagna[SUP] 3 4 [/SUP], Charles A Dinarello[SUP] 5 6 [/SUP], Antonio Abbate[SUP] 1 [/SUP]
Affiliations
Abstract
Interleukin (IL)-18 is a pro-inflammatory cytokine belonging to the IL-1 family, first identified for its interferon-γ-inducing properties. IL-18 regulates both T helper (Th) 1 and Th2 responses. It acts synergistically with IL-12 in the Th1 paradigm, whereas with IL-2 and without IL-12 it can induce Th2 cytokine production from cluster of differentation (CD)4[SUP]+[/SUP] T cells, natural killer (NK cells, NKT cells, as well as from Th1 cells. IL-18 also plays a role in the hemophagocytic lymphohistiocytosis, a life-threatening condition characterized by a cytokine storm that can be secondary to infections. IL-18-mediated inflammation was largely studied in animal models of bacterial, viral, parasitic, and fungal infections. These studies highlight the contribution of either IL-18 overproduction by the host or overresponsiveness of the host to IL-18 causing an exaggerated inflammatory burden and leading to tissue injury. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). The damage in the later phase of the disease appears to be driven by a cytokine storm, including interleukin IL-1 family members and secondary cytokines like IL-6. IL-18 may participate in this hyperinflammation, as it was previously found to be able to cause injury in the lung tissue of infected animals. IL-18 blockade has become an appealing therapeutic target and has been tested in some IL-18-mediated rheumatic diseases and infantile-onset macrophage activation syndrome. Given its role in regulating the immune response to infections, IL-18 blockade might represent a therapeutic option for COVID-19, although further studies are warranted to investigate more in detail the exact role of IL-18 in SARS-CoV-2 infection.
Keywords: COVID-19; IL-18; IL-1β; SARS-CoV-2; cytokine storm; infection.
. 2020 Aug 13.
doi: 10.1002/jcp.30008. Online ahead of print.
IL-18 and infections: Is there a role for targeted therapies?
Alessandra Vecchi?[SUP] 1 [/SUP], Aldo Bonaventura[SUP] 1 2 [/SUP], Stefano Toldo[SUP] 1 [/SUP], Lorenzo Dagna[SUP] 3 4 [/SUP], Charles A Dinarello[SUP] 5 6 [/SUP], Antonio Abbate[SUP] 1 [/SUP]
Affiliations
- PMID: 32794180
- DOI: 10.1002/jcp.30008
Abstract
Interleukin (IL)-18 is a pro-inflammatory cytokine belonging to the IL-1 family, first identified for its interferon-γ-inducing properties. IL-18 regulates both T helper (Th) 1 and Th2 responses. It acts synergistically with IL-12 in the Th1 paradigm, whereas with IL-2 and without IL-12 it can induce Th2 cytokine production from cluster of differentation (CD)4[SUP]+[/SUP] T cells, natural killer (NK cells, NKT cells, as well as from Th1 cells. IL-18 also plays a role in the hemophagocytic lymphohistiocytosis, a life-threatening condition characterized by a cytokine storm that can be secondary to infections. IL-18-mediated inflammation was largely studied in animal models of bacterial, viral, parasitic, and fungal infections. These studies highlight the contribution of either IL-18 overproduction by the host or overresponsiveness of the host to IL-18 causing an exaggerated inflammatory burden and leading to tissue injury. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). The damage in the later phase of the disease appears to be driven by a cytokine storm, including interleukin IL-1 family members and secondary cytokines like IL-6. IL-18 may participate in this hyperinflammation, as it was previously found to be able to cause injury in the lung tissue of infected animals. IL-18 blockade has become an appealing therapeutic target and has been tested in some IL-18-mediated rheumatic diseases and infantile-onset macrophage activation syndrome. Given its role in regulating the immune response to infections, IL-18 blockade might represent a therapeutic option for COVID-19, although further studies are warranted to investigate more in detail the exact role of IL-18 in SARS-CoV-2 infection.
Keywords: COVID-19; IL-18; IL-1β; SARS-CoV-2; cytokine storm; infection.