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THU0017 IN VITRO MECHANISTIC STUDIES DEMONSTRATE FILGOTINIB ACTIVITY THAT HAS POTENTIAL IMPLICATIONS FOR DIFFERENTIATION AMONG JAK INHIBITORS

Pei Han, Amy Meng, Nevena Mollova, Yuanjiang Yu, Julie A. DI Paolo
2019 Poster Presentations   unpublished
Results: In SLE patients respect to HC, plasma IL-1b levels were unmodified whereas IL-6 was higher, resulting significantly increased in SLE-S. Monocytes isolated from SLE patients released lower quantities of IL-1b after stimulation with BzATP, whereas the release of both IL-6 and TNF-a was significantly augmented in SLE-NS respect to both HC and SLE-S subjects after all types of stimulation. RT-PCR showed reduced P2X7R and augmented NLRP3 mRNA expression in SLE patients. Accordingly, P2X7R
more » ... ccordingly, P2X7R activity was significantly reduced in all SLE patients and did not appear to be influenced by a chloroquine pre-treatment. Conclusion: In SLE patients, compared to HC subjects, we found reduced P2X7R mRNA expression, increased NLRP3 mRNA, as a possible compensating mechanism, and correspondingly, significantly lower BzATP-induced intracellular Ca 2+ increase, without an apparent influence by chloroquine, one of the drugs most diffusely used for SLE treatment. The in vitro IL-1b release was reduced, whereas plasma IL-1b was unaltered, indicating an alternative source, other than monocytes, of this cytokine. Conversely, IL-6 and TNF-a levels were increased in vitro, and IL-6 was present in plasma at higher levels. The possible consequences of reduced P2X7R, mainly on cytokines network deregulation and lymphocyte proliferation, will be further investigated as well as the role of IL-6 and TNF-a as possible therapeutic targets.
doi:10.1136/annrheumdis-2019-eular.3361 fatcat:kl7wylv4uffq7gnm2ztujlxmam