L6 Cheat sheet Flashcards
What are some key articular cells involved in the pro-inflammatory actions of TNF in rheumatoid arthritis?
Monocytes, T cells, B cells, NK cells, neutrophils, mast cells, synovial fibroblasts, and osteoblasts.
What do articulatr cells refer to
refers to the important types of cells found within or around a joint (play a role in joint function, maintenance and inflammation in disease)
When was the first anti-TNF drug approved for rheumatoid arthritis?
1998
how effective are anti - TNF drugs for treating rheumatoid arthritis
effective
what are the main functions of TNF in rheumatoid arthritis
↑ Monocyte activation, cytokine release
↑ Neutrophil priming, oxidative burst, apoptosis
↑ Inappropriate T cell activation and apoptosis
↑ Endothelial cell expression of adhesion molecules (e.g. ICAM-1 and VCAM-1)
↑ Fibroblast MMP (MMP1, MMP3, MMP13) and cytokine release
What are some key articular cells involved in the pro-inflammatory actions of IL-6 in rheumatoid arthritis?
monocytes, macrophages, B cells, Mast cells, Synovial fibroblasts
how effective are anti IL_6 drugs for treating rheumatoid arthritis
effective `
when was the first anti IL-6R drug approved for rheumatoid arthritis
2010
which drugs related to IL_6 and rheumatoid arthritis are currently in clinical trial
anti IL-6 drugs (in clinical trials) and sgp130-fc (early clinical trial)
what are the main functions of IL-6 in rheumatoid arthritis
↑ B cell proliferation and antibody production
↑ T cell proliferation, differentiation, trafficking, effector function and survival
↑ Hepatic acute-phase response (systemic inflammation)
↑ Angiogenesis (↑ VEGF expression)
↑ Osteoclast (bone resorbing cell) differentiation via induction of RANKL expression
↑ Fibroblast MMP and cytokine release
What are some key articular cells involved in the pro-inflammatory actions of IL-17 in rheumatoid arthritis?
Th17 cells, ɣδ T cells (gamma delta T cells), NK and NKT cells
and Synovial fibroblasts
how effective are anti IL-17 drugs in clinical trials against rheumatoid arthritis
low efficacy (although effective for psoriatic arthritis)
what are current trials testing for in terms of IL-17 and rheumatoid arthritis
Current trials testing efficacy in patients that show poor response to anti-TNF
what are the main functions of IL-17 in rheumatoid arthritis
↑ Leukocyte recruitment (e.g. neutrophils)
↑ Osteoclast differentiation (osteoclastogenesis) via induction of RANKL expression
↑ Fibroblast MMP (MMP1, MMP9, MMP13) and cytokine release
↑ Angiogenesis
What are some key articular cells involved in the pro-inflammatory actions of IL-1 in rheumatoid arthritis?
Monocytes, B cells, Synovial fibroblasts and chondrocytes
when was Anakinra ( Engineered version of soluble IL-1R antagoinst) first approved for rheumatoid arthritis
2002
how effective are anti IL-1 drugs against rheumatoid arthritis
Not recommended. Limited use due to lower efficacy than other biological drugs
What does the failure of IL-1 blockade in rheumatoid arthritis suggest about its role in synovial processes?
The failure does not imply IL-1 lacks a functional role in synovial processes but rather that it does not play a pivotal regulatory role in the inflammatory cascade. Many effector pathways leading to symptoms are potentially mediated by IL-1, often working synergistically with TNF. These include prostanoid synthesis and the activation of chondrocytes and fibroblast-like synoviocytes (FLSs).
What are some key articular cells involved in the pro-inflammatory actions of RANKL in bone erosion / rheumatoid arthritis?
Osteoblasts, CD4+ T cells (Th17, Th1 cells, synovial fibroblasts)
what have phase II trials shows about anti RANKL
that it is safe and limits progression of joint destruction
what is the main function of RANKL
↑ Bone resorption via osteoclast differentiation, maturation and activation.
What are osteoclasts and how do they function?
Osteoclasts stick to and digest underlying bone minerals by releasing acids and collagenases.
What is the process by which osteoclasts differentiate?
through a cytokine driven process
What are the essential cytokine mediators involved in osteoclast differentiation?
The essential cytokine mediators are RANKL (Receptor Activator of Nuclear Factor-κB ligand) and M-CSF (Macrophage Colony-Stimulating Factor), expressed by synovial fibroblasts and T helper cells.
What cytokines support osteoclast differentiation?
TNF (Tumour Necrosis Factor), IL-1 (Interleukin-1), IL-17 (produced by TH17 cells), and IL-7 (produced by synovial fibroblasts) support osteoclast differentiation.
Which cytokines inhibit osteoclast differentiation?
IL-4, IL-10, GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor), and IFNγ (Interferon-gamma) inhibit osteoclast differentiation.
What role do TH cells play in osteoclast differentiation?
T helper cells produce cytokines that either support or inhibit osteoclast differentiation, with TH1 cells producing RANKL, M-CSF, TNF, IL-1, GM-CSF, and IFNγ, and TH17 cells producing IL-17.
How does osteoclast differentiation differ in rheumatoid arthritis?
In rheumatoid arthritis, the differentiation of osteoclasts from haematopoietic osteoclast precursors is driven by cytokines like RANKL and M-CSF, with additional cytokines like TNF, IL-1, and IL-17 playing a key role in the process.
