4.2. IL-1
IL-1 that include IL-1α and IL-1β is also an important inflammatory
cytokine. IL-1α is released from dying epithelial and endothelial cells,
while IL-1β comes from activated macrophages, monocytes, and
neutrophils. IL-1 is primarily associated with acute and chronic
inflammation. In the inflammatory cascade, IL-1 is an upstream cytokine
that promotes the activation of other cytokines including IL-6 and TNF
-α (Nieto-Torres et al., 2014).
IL-1 receptor (IL-1R) antagonists have also been used in trial treatment
in COVID-19 patients. Anakinra is a protein inhibitor of IL-1R. In
COVID-19 patients with respiratory insufficiency and hyperinflammation,
pneumonia, or ARDS, application of anakinra significantly reduced the
mortality (Cavalli & Dagna, 2021; Franzetti et al., 2021; Pontali et
al., 2021). Intravenous administration of anakinra (5 mg/kg twice a day)
can significantly decrease serum CRP and improve respiratory function in
COVID-19 patients with ARDS (Cauchois et al., 2020; Cavalli et al.,
2020). Subcutaneous application of anakinra (100 mg twice a day for 72
h, then 100 mg daily for 7 days) also decreased the mortality in
COVID-19 patients with respiratory improvement (Huet et al., 2020).
Similarly, the human IL-1R monoclonal antibody, canakinumab can
attenuate the systemic inflammation and improve respiratory function in
patients with bilateral pneumonia and hyperinflammation after SARS-CoV-2
infection (Ucciferri et al., 2020).
The development of cytokine antagonists is good strategy, and this type
of drugs might benefit patients in reducing the specific cytokine
induced inflammatory damage. However, cytokine storm induced by
SARS-CoV-2 involves multiple cytokines, it is impossible for one
cytokine antagonist to block all the inflammatory responses. Anyway,
cytokine antagonists have shown some benefit in reducing symptoms and
are deserved to be evaluated in the treatment of COVID-19.