Anti-Cytokine Therapy Flashcards
Which two vasoactive amines are chemical mediators of inflammation?
Histamine and 5-HT
Lipid-derived arachidonic acid metabolites are chemical mediators of
Inflammation
Which cytokines are chemical mediators of inflammation?
IL-1 and TNF-a
What are 4 chronic inflammatory cells and mediators?
Macrophages, lymphocytes, eosinophils, and mast cells
What are the four main diseases associated with chronic autoimmune inflammation?
- ) RA
- ) Crohn’s/Colitis
- ) Psoriasis
- ) Lupus
Anti-cytokine therapy is valuable for treating
Chronic autoimmune inflammation
In RA, inticing antigen drives lymphocyte proliferation production of
Rheumatoid factor autoantibody
Then, fixation of complement amplifies the destructive cascade and attracts inflammatory cells, resulting in production of
Cytokines and enzymes
Binds TNF-a with high affinity and neutralizes its biological activity
Etanercept (ENBREL)
Recombinant fusion protein consisting of two soluble p75 TNF receptor moieties linked to Fc portion of human IgG1
Etanercept (ENBREL)
Chimeric monoclonal antibody to TNF-a
-Fc region of human IgG and Fab sequences of a mouse anti-TNF-a antibody
Infliximab (Remicade)
Reduces blood level of TNF-a and may dislodge TNF-a bound to cells
Infliximab (Remicade)
Infliximab (Remicade) is used to treat?
Crohn’s and RA
Recombinant human monoclonal antibody to TNF-a
Adalimumab (Humira)
Complexes with soluble TNF-a and prevents its interaction with p55 and p75 cell surface receptors
Adalimumab (Humira)
Adalimumab (Humira) is used to treat
RA
Genetically engineered antibodies that are typically 33% mouse protein and 67% human protein
Chimeric and humanized antibodies
Recombinant non-glycosylated IL-1 receptor antagonist (IL-1Ra)
-an endogenous protein
Anakinra (Kineret)
Blocks the cellular effects of IL-1
Anakinra (Kineret)
Anakinra (Kineret) is used to treat?
RA
The pathogenesis of RA activates the
Innate immune system
Dendritic cells then migrate to the
Lymph node
Here, the DCs present antigens to
T cells
T cells then proliferate and migrate to the
Joint
Here, T cells produce pro-inflammatory
Cytokines
Activated macrophages and fibroblasts then produce
TNF-a
A humanized monoclonal antibody that competitively inhibits the binding of IL-6 to its receptors
Tocilizumab (Actemra)
Tocilizumab (Actemra) is used to treat
RA
A pro-inflammatory cytokine that is overproduced in patients with RA and contributes to joint cell destruction
IL-6
Fusion protein of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to IgG1
Abatacept (Orencia)
Inhibits binding of CD80 and 86 to CD28, preventing T-cell activation and lowering serum concentration of inflammatory markers, cytokines, and rheumatoid factor
Abatacept (Orencia)
Used to treat patients with moderate to severe RA who have not responded to one or more DMARD
Abatacept (Orencia)
Inflammatory bowel disease of the entire GI tract
-chronic intestinal inflammation
Crohn’s disease
Led to development of novel agents that specifically block key cytokines (i.e. infliximab)
Crohn’s disease
PEGylated Fab fragment of humanized TNF-a antibody
Certolizumab (Cimzia)
Binds to soluble and membrane bound TNF-a
Certolizumab (Cimzia)
Used to treat moderate to severe RA in adults with inadequate response to conventional therapy
Certolizumab (Cimzia)
What are the three therapeutic targets of psoriasis?
IL-17A, 12, and 23
A fully human IgG1 antibody directed against the p40 subunit of IL-12 and IL-23 cytokines which are present in psoriasis skin lesions
Ustekinumab (Stelara)
What are three treatments that target IL-17A to treat psoriasis?
Secukinumab (Cosentyx), Ixekizumab (Taltz), and Brodalumab (Siliq)
Injectable human IL-17A antagonists
Secukinumab (Cosentyx), Ixekizumab (Taltz), and Brodalumab (Siliq)
Has a boxed warning about suicidal ideation nd behavior and is only available through REMS
Brodalumab (Siliq)
A monoclonal antibody to BAFF/BLyS
-first new drug for lupus in >50 years
Benlysta
Key determinant of whether B cell will survive or die during development of tolerance
B-cell Activating Factor (BAFF/BLyS)
B-cell Activating Factor (BAFF/BLyS) is a member of the
TNF-a family of proteins
One of the adverse effects to anti-cytokine therapy is reactions at the
Injection sites
We can see cytopenias with
Anti-TNF therapy
Ibfliximab carries a risk of
Hepatotoxicity
Very expensive
Anti-cytokine therapy
An active infection, positive TB test, and pre-existing demyelinating disorders are
Contraindications to anti-cytokine therapy
Once thought to be simply the malignant growth of cells
-fueled by inflammation and localized immunosuppression
Cancer
The FDA has recently approved the 1st drug for moderate and severe Eczema cases. This drug is called dupilumab and it targets
IL-4Rα
The first drug approved (2017) for multiple sclerosis
Ocrelizumab
An anti-CD20 antibody that was approved for primary progressive MS
Ocrelizumab
Biologic agents for severe eosinophilic asthma target
IL-5
What are the two humanized IL-5 antagonists to treat eosiniphilic asthma?
Mepolizumab (Nucala), Reslizumab (Cinqair),
A humanized monoclonal antibody selective for the IL-5 receptor
Benralizumab (Fasenra)
Mepolizumab (Nucala) is injecyed
Subcutaneously
