4.1 IL-6 inhibitor
Coordinated cytokine response is a necessary condition for host immune
response. Nevertheless, uncoordinated response results in excessive
inflammation in some patients infected with COVID-19. The concentration
of cytokines, granulocyte-macrophage colony stimulating factor and
interleukin-6 in plasma are higher than in non-infected people. This not
only suggests that cytokine secretion is related to the severity of the
disease, but also indicates that inhibition of excessive inflammatory
response may be an adjuvant therapy for COVID-19 (Guan, Ni, Hu, Liang,
Ou, He, Liu, Shan, Lei, Hui, Du, Li, Zeng, Yuen, Chen, Tang, Wang, Chen,
Xiang, Li, Wang, Liang, Peng, Wei, Liu, Hu, Peng, Wang, Liu, Chen, Li,
Zheng, Qiu, Luo, Ye, Zhu, Zhong, et al., 2020). A clinical result from
Chinese research reveals that IL-6 may probably be a key to this
inflammation (F. Zhou et al., 2020). Therefore, it may reverse this
process and improve clinical conditions to direct monoclonal antibodies
towards IL-6.
Tocilizumab, an interleukin-6 (IL-6) receptor blocking antibody, serves
as an inhibitor to IL-6-mediated signal transduction hence control
inflammation (Le et al., 2018). An early clinical report revealed that
91% of 21 patients with COVID-19 showed improvement in respiratory
function and decline in fever after taking tocilizumab. Preliminary data
showed that tocilizumab reduced mortality. It provides immediate
improvement severe cases of COVID-19. Tocilizumab treatment resolved
symptoms, such as hypoxemia and CT shadow changes (X. Xu et al., 2020).
Mechanistically, tocilizumab regulates IL-6 thereby promote the release
of inflammatory cytokines. It is therefore an effective drug for
treating patients with severe COVID-19 (Zhang, Wu, Li, Zhao, & Wang,
2020).
Currently, multiple randomized controlled trials for single or combined
use of tocilizumab in patients with COVID-19 complicated with severe
pneumonia are ongoing in keeping with the Chinese national treatment
guidelines (Sanders et al., 2020). For example, Some administrations
also study Tocilizumab with favipinavir, in order to realize the
potential synergistic effect of the two drugs (NCT04310228).
Furthermore, it should also be noted the potential adverse drug
reactions. Tocilizumab can increase the risk of infections, especially
infections of the upper airways. It can also pose risk of AST
transaminases, hypertension, hematological effects, hepatotoxicity,
gastrointestinal perforation, hypersensitivity reactions to the active
principle (Sheppard, Laskou, Stapleton, Hadavi, & Dasgupta, 2017).