4.2 Other Inhibitors for cytokine storm
After the body is infected with the virus (e.g., respiratory syncytial
virus), natural immunity (e.g., NK cells, macrophages) occurs within 1-3
days after infection, and then the activated immune cells will release
many cytokines (e.g., interleukins, interferon) within 4-7 days, which
can activate more immune cells through cascade amplification, even
include T cells and B cells. In the final stage (Days 7-9), B cells may
become mature and will produce some specific antibodies, or neutralizing
antibodies, which can control the virus as soon as possible. In
addition, the immune response of specific T cells can also control the
virus (Openshaw & Tregoning, 2005). Antibodies and cytokines produced
through immune activation can attack viruses. At the same time, these
cytokines and activated immune cells will reach various organs with
blood circulation. Once this attack is too aggressive, it is easy to
attack its own substances as foreign substances, which then cause damage
to organs. Therefore, when dealing with viruses, we should also pay
attention to the treatment of excessive immune response. Otherwise the
damage to the body still exists. Currently, new methods for treating
cytokine storms can be achieved through the following main inhibitors:
IL-1 inhibitors, IL-6 inhibitors (mentioned above), GM-CSF inhibitors,
and JAK inhibitors.
A retrospective study on IL-1 antagonists (Anakinra) indicated that
among moderate-to-severe ARDS, and hyperinflammation patients (aged ≥18
years) with COVID-19, 29 of them used high doses of IL-1 antagonists. 16
people were enrolled in the reference group. It can be seen that after
21 days of treatment, the group using the IL-1 receptor antagonist had a
10% mortality rate, and the reference group was 44%, indicating that
IL-1 antagonist can reduce the mortality rate (Cavalli et al., 2020). In
addition to anakinra, other anti-IL-1 antibodies, such as canakinumab,
are also undergoing clinical trials.
The study found that there were two cytokines increased in novel
coronavirus patients, one is IL-6, and the other is GM-CSF. An
open-label clinical trial on the anti-GM-CSF receptor antibody,
Mavrilimumab, revealed that among the severe patients without invasive
ventilator, the experimental group was 13 people, and the control group
was 26 people, then after 14 days treatment, 85% of the treatment group
had improved clinical symptoms, and the control group was lower, only
42% improved. The key data was that there was zero death in the
treatment group and 27% in the control group. In addition, the
mortality rate of patients using mechanical ventilation is 8% in the
treatment group and 35% in the control group, so the treatment also
reduces this rate(Y. Zhou et al., 2020).