4.3 Side effects
As the application of JAK inhibitor in ARDS barely started in the resent
years, the side effects are almost revealed in the usage of treating
other immune related disease such as IBD and RA. Pan-JAK inhibitors
block a broad of cytokines, ILs, IFNs, hormones and growth factors.
Widely inhibition of the upon factors contribute to many adverse events
ranges, such as infections, hematological or cardiovascular affects,
malignancies, and gastrointestinal perforations.
Since blockage of many cytokines in host defense, infections become a
common adverse event of JAK inhibitors. One common infection in
tofacitinib and baricitinib treated patients is reactivation of
varicella zoster virus. The exact mechanism is unclear: inhibit IFN
production may cause impairment of anti-viral immunity(Favalli,
Biggioggero, Maioli & Caporali, 2020). In addition, inhibition of JAK1
and JAK3 reduced the NK, innate lymphoid and CD8+T cells in numbers and
functionally. The possibility of diverticulitis is another disadvantage
of JAK inhibitors(Jamilloux, El, Vuitton, Gerfaud-Valentin, Kerever &
Seve, 2019).
Moreover, JAKs especially JAK2 lead to hematological effects (decreasing
of lymphocytes, NK cells, neutrophils, platelets, and
anemia)(Wollenhaupt et al., 2019). The decreasing of hemoglobin probably
related to inhibition of EPO or other JAK2 related cytokines. There are
also study shows that JAK inhibitors increase the high- and low-density
lipoproteins and thromboembolic evens(Rao et al., 2015). The underling
mechanism or whether it is related to cardiovascular effects is not
clearly studied until now. Additionally, due to the blockage of IL-6
signaling, pan-JAK inhibitor is reported increasing the property of
gastrointestinal perforation.