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.