Anticytokines Flashcards
what do rheumatoid arthritis, inflammatory bowel disease (Crohn’s, ulcerative colitis), psoriasis, and psoriatic arthritis have in common, regarding cause and potential therapy
chronic autoimmune inflammation
anti-cytokine therapy can be therapeutic
how are soluble receptor antagonists such as etanercept used against TNF-alpha
fuse Fc of antibody with piece of TNF-a receptor (fusion protein)
binds TNF-a in circulation and acts as a sponge to soak it up
use of
a. infliximab
b. adalimumab
c. ustekinumab
d. secukinumab
remember -mab = monoclonal antibody
these are therapeutic antibodies or antibodies fragments that target cytokines
infliximab, adalimumab: target TNF-alpha
ustekinumab: targets IL-12/23
secukinumab: targets IL-17A
function of tocilizumab and sarilumab?
remember -mab = monoclonal antibody
therapeutic antibody to IL-6 receptor
*Too Soon for all these acute phase inflammation proteins from the liver! (induced by IL-6),
T = Tocilizumab
S = Sarilumab
anakinra
recombinant non-glycoslyated IL-1 receptor antagonist (anti-cytokine therapy)
recombinant form of an endogenous protein, targets cytokine receptor
translate meaning of each of these therapeutic antibody suffixes:
a. -omab
b. -ximab
c. -zumab
d. -umab
a. -omab = murine
b. -ximab = chimeric (mostly human)
c. -zumab = humanized (90%)
d. -umab = 100% human
highest potential for immunogenicity with -omab (murine), lowest with -umab (human)
adalimumab and infliximab both target TNF-alpha
based on their nomenclature, describe their difference
-mab = monoclonal antibody
-umab = human (adalimUMAB is human mAb)
-ximab = chimeric (infliXIMAB is chimeric mAb) - Fc region of human IgG and Fab sequence of mouse anti-TNF-alpha antibody
*both target TNF-alpha
DMARDs
disease-modifying anti-rheumatic drugs: anti-cytokine therapy for rheumatoid arthritis (autoimmune inflammation)
csDMARDs (Conventional Synthetic): prevent proliferation of lymphocytes
bDMARDs (Biologic): target cytokine pathways (TNF-alpha, IL-1)
—> examples: etanercept, adalimumab, infliximab, anakinra
what cytokines are unhinged in inflammatory bowel disease such as Crohn’s and ulcerative colitis? (4)
TNF-a: inflammation, NFkB and c-JUN expression
IL-6: inflammation, acute phase proteins from liver
IL-12: activates NK cells
IL-23: Th17 differentiation (—> neutrophil activation)
the following biological agents target TNF-alpha, describe how:
a. etanercept
b. infliximab
c. adalimumab
d. golimumab
e. certolizumab
a. etanercept: soluble receptor fusion protein, binds TNF-a
b/c/d: infliximab (*Crohn’s), adalimumab, golimumab: mAb to TNF-a, binds soluble and transmembrane TNF-a
e. certolizumab: PEG conjugated Fab fragment, binds TNF-a
*all treat rheumatoid arthritis
*remember: Eat Crap, Get Acute Inflammation (like that caused by TNF-alpha!)
E = Etancercept
C = Certolizumab
G = Golimumab
A = Adalimumab
I = Infliximab
tocilizumab and sarilumab
mAb to IL-6 receptor (blocks binding)
bind both soluble and transmembrane form of receptor
ustekinumab is a mAb to the common subunit of IL ___ and ____
and is indicated in treatment for ____
ustekinumab: mAb against common subunit of IL-12 and IL-23 (p40 subunit)
indicated in treatment for psoriasis
tildrakizumab and guselkumab are biological agents that act as mAb to ___ subunit of IL-23, thereby binding the cytokine
and are used in treatment for ____
tildrakizumab and guselkumab are mAb to p19 subunit of IL-23, treat psoriasis
secukinumab, ixekizumab, and brodalumab treat ____ by binding or blocking action of IL-____
treat psoriasis, bind/block IL-17A
secukinumab: bind IL-17A
ixekizumab: bind IL-17A
brodalumab: block IL-17A binding (mAb to receptor)
how does abatacept treat rheumatoid arthritis
blocks co-stimulation of T cells by inhibiting B7 binding to CD28
fusion protein of CTLA-4 (cytotoxic T lymphocyte associated antigen) linked to IgG1
aba[T cell]a[interCEPTion]
