Tarted recruitmentIFN Sort IIIFN Variety III Common IFN method: Target plasmacytoid dendritic cellsNo trials identifieddaxdilimab VIB7734, phase 1, completed, Butachlor In Vitro results awaited VIB7734 BIIB059, key endpoints met in phase 2 NCT02847598). Phase three ongoing, NCT04895241 Infliximab, considered risky, investigated in open label NCT00368264 [8]. Benlysta, approved, postregistration studies ongoing Ianalumab/OP0302 (VAY736) ongoing phase 2, NCT03656562, results awaited. Rozibafusp alfa (AMG 570), results awaited, phase two, NCT04058028 Tabalumab (LY 2127399), major endpoints not met in phase 3, NCT01196091 Atacicept, main endpoints not met in phase three, NCT00624338 Blisibimod (AMG 623/A-623), major endpoints not met, phase three, NCT02443506 Telitacicept, RC18, Phase 2, NCT02885610 Recombinant Human Interleukin-2, constructive results, Phase twoHe:2020cn NCT02465580 and NCT02932137 A number of substances: NKTR-358 (LY3471851), ILT-101 and much more, Phase 1 and two, NCT03556007, NCTTNF-Blys/BAFF/APRILIL-Int. J. Mol. Sci. 2021, 22,four ofTable 2. Cont. Cytokine Target Drug/Molecule and Outcomes from Clinical TrialsIL-MRA 003 US Ongoing phase 1 NCT00046774 Ala-Cpn10 Ongoing phase 1 and 2 NCT01838694 Vobarilizumab (ALX-0061) Completed phase two, NCT02437890 Sirukumab (CNTO 136) Completed phase 1, NCT01702740, not further investigated PF 04236921, completed phase 2, key endpoint not met, NCTIL-10 IL-16 IL-17 IL-12, IL-BT 063, Phase 2 completed, results unavailable, NCT02554019 Not identified Sekucinumab, Phase three recruiting, NCT04181762 Ustekinumab, major endpoints met in phase 2a, NCT02349061. Phase three is ongoing, NCTIL-21 IL-1 IL-18 IL-NNC0114-0006, Phase 1, NCT01689025 BOS161721 (avizakimab). Completed phase 1 and two, final results awaited NCTAnakinra, only case reports Not identified Not identifiedFigure 1. Cytokines connected with SLE pathogenesis are shown and arrows indicates the primary producer or the primary target cell.2. Interferons Interferons (IFNs) are pro-inflammatory cytokines produced in response to infections, as a part of the host defense by the innate immune method. Within the human physique, 3 varieties of IFNs are known to be produced and all look to possess function in SLE: form I, II and III. The sort I IFNs incorporate 17 subtypes of IFN-s, also IFN-, IFN-, IFN-, IFN-, IFN-,I FN- and IFN- [2].Int. J. Mol. Sci. 2021, 22,five ofThe IFN-s are the main effector cytokines of this variety and it really is probably the most studied in SLE. Expertise on IFN- and IFN- is also available, but other variety I IFNs are much less studied and viewed as of much less significance [3,9]. All IFN-s and single IFN- are ubiquitously expressed, though IFN- is a lot more organ distinct [10]. Essentially the most potent form I IFNs making cells are plasmacytoid dendritic cells [1,4]. All kind I IFNs signal through exact same receptor denoted IFNAR1/IFNAR2 [2]. There is only one particular kind II IFN–namely, IFN—which is primarily developed by CD4 or CD8 Th1 cis-4-Hydroxy-L-proline lymphocytes, as well as NK and B cells, as well as expert antigen presenting cells. The IFN- signal is transmitted through receptor composed of two subunits IFNGR1 and IFNGR2 [9]. 4 molecules, which belong to the type III IFN household, have been identified: IFN1, -2, -3 and -4. The main producers of IFN-1 are antigen presenting cells, but additionally epithelial cells [10]. Epithelial and mucosal surfaces are the key responders and expressers of IFN-1R/IL10R [3]. two.1. Form I IFNs in SLE two.1.1. IFN- It was described already in 1990 that administration of IFN- as a therapy for other illnesses, can induce SLE [11]. Later o.