Interleukin-1 beta, plasminogen activator and inhibitor of plasminogen activator in synovial fluid of rheumatoid arthritis, psoriatic arthritis and osteoarthritis

1994 ◽  
Vol 41 (1-2) ◽  
pp. 88-89 ◽  
Author(s):  
M. Pianon ◽  
L. Punzi ◽  
M. P. Stefani ◽  
N. Bertazzolo ◽  
M. Michelotto ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Synovial Fluid ◽  
Plasminogen Activator ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Inhibitor Of Plasminogen Activator

scholarly journals AB0108 IRAK4 INHIBITION SUPPRESSES PROINFLAMMATORY CYTOKINE PRODUCTION FROM HUMAN MACROPHAGES STIMULATED WITH SYNOVIAL FLUID FROM RHEUMATOID ARTHRITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1353.2-1353
Author(s):  
A. Yadon ◽  
D. Ruelas ◽  
G. Min-Oo ◽  
J. Taylor ◽  
M. R. Warr
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Signaling Pathways ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
Proinflammatory Cytokine Production ◽  
Human Macrophages ◽  
Percent Suppression

Background:Rheumatoid arthritis (RA) is characterized by chronic, uncontrolled joint inflammation and tissue destruction. Macrophages are thought to be key mediators in both the initiation and perpetuation of this pathology.1,2The RA synovium contains a complex inflammatory milieu that can stimulate macrophage-dependent production of proinflammatory cytokines through multiple signaling pathways.1,2Existing evidence indicates that toll-like receptors (TLRs) and interleukin-1 receptors (IL-1R) along with their agonists, damage-associated molecular patterns (DAMPs) and IL-1β, are highly expressed in RA joints and are important mediators of synovial macrophage activation and proinflammatory cytokine production.1-9IRAK4 (interleukin-1 receptor-associated kinase 4) is a serine/threonine kinase that facilitates TLR and IL-1R signaling in many cell types, including macrophages.10IRAK4 inhibition represents an opportunity to reduce proinflammatory cytokine production in the joints of patients with RA.Objectives:To investigate the effect of a highly selective IRAK4 inhibitor on proinflammatory cytokine production from human macrophages stimulated with synovial fluid from patients with RA.Methods:Primary human monocytes from 2 independent donors were differentiated for 6 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) to generate human monocyte-derived macrophages (hMDMs). hMDMs were then pretreated with an IRAK4 inhibitor for 1 hour and subsequently stimulated for 24 hours with RA synovial fluid from 5 patients. Culture supernatants were then assessed for secretion of proinflammatory cytokines by MesoScale Discovery.Results:RA synovial fluid stimulation of hMDMs resulted in the production of several proinflammatory cytokines, including IL-6, IL-8, and TNFα. Pretreatment of hMDMs with an IRAK4 inhibitor resulted in the dose-dependent inhibition of IL-6, IL-8, and TNFα production, with an average EC50± SD of 27 ± 31, 26 ± 41, and 28 ± 22 nM, respectively. Maximal percent suppression ± SD of IL-6, IL-8, and TNFα were 76 ± 8.8, 73 ± 15, and 77 ± 13, respectively. To evaluate the specific IRAK4-dependent signaling pathways mediating this response, hMDMs were pretreated with inhibitors of TLR4 (TAK242) and IL-1R (IL-1RA) prior to stimulation with RA synovial fluid. Both TAK242 and IL-1RA inhibited proinflammatory cytokine production. For TAK242, maximal percent suppression ± SD of IL-6, IL-8, and TNFα were 39 ± 25, 48 ± 24, and 50 ± 21, respectively. For IL-1RA maximal percent suppression ± SD of IL-6, IL-8, and TNFα were 18 ± 18, 20 ± 23, and 16 ± 18, respectively. The broad range of inhibition across each stimulation highlights the complexity and variability in the signaling pathways mediating proinflammatory cytokine production from hMDMs stimulated with RA synovial fluid, but demonstrates that RA synovial fluid can stimulate proinflammatory cytokine production in hMDMs, at least partly, through IRAK4-dependent pathways.Conclusion:This work demonstrates that IRAK4 inhibition can suppress proinflammatory cytokine production from macrophages stimulated with synovial fluid from patients with RA and supports a potential pathophysiological role for IRAK4 in perpetuating chronic inflammation in RA.References:[1]Smolen JS, et al.Nat Rev Dis Primers.2018;4:18001.[2]Udalova IA, et al.Nat Rev Rheumatol.2016;12(8):472-485.[3]Joosten LAB, et al.Nat Rev Rheumatol.2016;12(6):344-357.[4]Huang QQ, Pope RM.Curr Rheumatol Rep.2009;11(5):357-364.[5]Roh JS, Sohn DH.Immune Netw.2018;18(4):e27.[6]Sacre SM, et al.Am J Pathol.2007;170(2):518-525.[7]Ultaigh SNA, et al.Arthritis Res Ther.2011;13(1):R33.[8]Bottini N, Firestein GS.Nat Rev Rheumatol.2013;9(1):24-33.[9]Firestein GS, McInnes IB.Immunity.2017;46(2):183-196.[10]Janssens S, Beyaert R.Mol Cell.2003;11(2):293-302.Disclosure of Interests:Adam Yadon Employee of: Gilead, Debbie Ruelas Employee of: Gilead, Gundula Min-Oo Employee of: Gilead, James Taylor Employee of: Gilead, Matthew R. Warr Employee of: Gilead

Differential diagnosis between rheumatoid arthritis and psoriatic arthritis: the value of ultrasound findings at metacarpophalangeal joints level

2011 ◽  
Vol 70 (6) ◽  
pp. 1111-1114 ◽  
Author(s):  
Marwin Gutierrez ◽  
Emilio Filippucci ◽  
Fausto Salaffi ◽  
Luca Di Geso ◽  
Walter Grassi
Keyword(s):  
Rheumatoid Arthritis ◽  
Differential Diagnosis ◽  
Psoriatic Arthritis ◽  
Synovial Fluid ◽  
Potential Role ◽  
Power Doppler ◽  
Extensor Tendon ◽  
Synovial Hypertrophy ◽  
Ultrasound Findings

ObjectiveTo investigate the potential of ultrasound (US) in the differential diagnosis between rheumatoid arthritis (RA) and psoriatic arthritis (PsA) at metacarpophalangeal (MCP) joints level.Methods18 RA patients and 20 PsA patients with clinical involvement of MCP joints were included. All US examinations were performed by two rheumatologists investigating: presence of joint cavity widening (JCW), synovial fluid and/or synovial hypertrophy, peritenon extensor tendon inflammation (PTI) and intra-articular or peri-tendinous power Doppler (PD) signal.ResultsA total of 83 MCP joints in 18 RA patients were assessed. In all of these the authors found different degrees of JCW. 15 of 83 (18%) MCP joints showed synovial fluid, whereas 68 of 83 (82%) MCP joints showed synovial hypertrophy. In 72 of 83 (86.7%) MCP joints intra-articular PD was detected. No PTI pattern was found in these patients.In PsA patients, a total of 82 MCP joints in 20 patients were assessed. 54 of 82 (65.8%) MCP joints showed PTI pattern (p = 0.001). In 50 of these 54 (92.5%) MCP joints extra-articular PD signal was detected (p = 0.001). 28 of 82 (34.1%) MCP joints showed different degrees of JCW. 6 of 28 (21.4%) MCP joints presented synovial fluid, whereas 22 of 28 (78.5%) MCP joints showed synovial hypertrophy. In 8 of 82 (9.7%) MCP joints the JCW and PTI patterns were found contemporaneously.ConclusionsPreliminary results demonstrate that PTI pattern is a higher characteristic of PsA, which suggests a potential role of US in the differential diagnosis between RA and PsA at MCP joints level.

scholarly journals Value of synovial fluid interleukin-1 beta determination in predicting the outcome of psoriatic monoarthritis.

1996 ◽  
Vol 55 (9) ◽  
pp. 642-644 ◽  
Author(s):  
L Punzi ◽  
N Bertazzolo ◽  
M Pianon ◽  
E Rizzi ◽  
P Rossini ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Interleukin 1 ◽  
Interleukin 1 Beta
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