pathophysiology Flashcards
inflammation: recognise the role of prostaglandins and inflammatory molecules (including cytokines, gamma-interferon, interleukins and TNF-alpha) in mediating inflammation, recall the scientific basis for the use of TNF-alpha inhibitors and prostaglandin blockade in rheumatic disease
what cell can produce different cytokines, and what are their effect
T cells and macrophages, causing macrophage, B and T cell activation
what is the dominant pro-inflammatory cytokine in rheumatoid synvoium and is therefore inhibited in treatment
TNF-a
8 actions of TNF-a in synovium
proinflammatory cytokine release, PGE2 production, osteoclast activation, chondrocyte activation, angiogenesis, leukocyte accumulation, endothelial cell activation, chemokine release, hepcidin induction
what cytokines will take over from TNF-a if TNF-a inhibited, and therefore also have a clinically available blockade
IL-1, IL-6
what else can be done in addition to cytokine blockade when treating rheumatoid arthritis
deplete B cells by parenteral (i.v.) administration of antibody against B cell surface antigen CD20
what other cytokine is important in bone destruction in rheumatoid arthritis
RANKL
what cells produce RANKL in rheumatoid arthritis, and function
produced by T cells and synovial fibroblasts, acting to stimulate osteoclast formation by binding to RANK on osteoclast precursors
what is a monoclonal antibody against RANKL, and what is it used to treat
denosumab, used for treatment in osteoporosis, bone metastases, multiple myeloma and giant cell tumours
what is a key feature of systemic lupus erythematosus, and is therefore targeted
B cell hyper-reactivity
2 biological treatments of systemic lupus erythematosus
rituximab, belimumab
how does rituximab help treat systemic lupus erythematosus
chimeric anti-CD20 antigen antibody used to deplete B cells
how does belimumab help treat systemic lupus erythematosus
recombinant fully human IgG1 monoclonal antibody against B cell survival factor (BLYS); inhibits this, resulting in impaired B cell survival and reduced B cell numbers
what do other biological therapies for systemic lupus erythematosus
antigens, B cell survival factors, B cell receptors, IL, complement
what are prostaglandins
lipid mediators of inflammation that act on platelets, endothelium, uterine tissue and mast cells
what are prostaglandins synthesised from
essential fatty acids
