Cytokines Flashcards
Function of cytokines
Immune & inflammatory response
Haemotopoiesus (production of RBC)
Wound healing
Cytokines produced by
WBC (not a gland) & function in auto run fashion
EPO
Cytokine produced by kidney & liver, acts in endocrine manor to promote RBC production in bone marrow aka true hormone
EPO Function
Stimulate RBC in anaemia people
Growth factors
Promote wound healing
Neurotrophic factors
Abatement of neurodegenerative diseases
Pro inflammatory cytokines include
IL-1
IL-6
IL-8
TNF
Involved in pathogenicity of septic shock & RA
Interferons IFN-a IFN-b IFN-y functions
-Induce cellular resistance to viral attack
-Regulate most aspects of immune function
-Regulate growth & differentiation of many cells
-Sustenance of early phase of pregnancy
IFN-a IFN-b
Type-1 Interferons
30% aa identity
Bind to same receptor
Induce similar biological activities
Aka acid stable interferons
IFN-y
Type ll Interferon
Binds to separate receptors & induce diff range of biological activity than a,b
Type l Interferon
-antiviral activity
- anti-proliferative effect on tumours & cells
-anti tumour effects: due to increase in NK & T-cytotoxic cell activity, which recognise & kill cancer cells
Type ll Interferon
-IFN-y has weak antiviral, anti proliferative activity
- co admin with type l gives antiviral & anti proliferative effect of a/b
IFN-y promotes
Growth & differentiation in cells that include immune & inflammatory responses
Main macrophage activating factor
IFN-y macrophage mediated effects
-destruction of invading microbes
-destruction of intracellular pathogens
-tumour cytotoxicity
-increased major histocompatibility complex MHC antigen expression-> enhanced activity of lymphocytes
Interferon biotech
Identified 1950
Initially impractical: low levels produced in body
Large scale purification, not viable
Exhibit species preference human-human
Interferons 1970s
In small quantities
From human leukocytes from transfused blood supplies
Prep was only 1% pure
Consisted on various IFN-as (15+)
Large scale interferon production
Mammalian cell culture
Cancer cell lines secret larger amounts of IFN
Good for large scale culture due to transformed nature
Interferon biotech
Namalwa Cell line
Tradename: Wellferon
First approved
9 IFN-a pure subtypes
Human lymphoblastoid cells
Cells propagated up to 8000L
Addition of Sendai virus
Result: significant quantities of leukocyte interferon
1980 y-immunex
Recombinant DNA
Large quantity
Pure interferon, only one subtype
(rh) produced by E.coli
Lacks PTM compensates that IFN-a/b are normally not glycosolated
IFN-y: is glycosolated, e.coli unglucosolated similar to native human protein
Production & medical use of IFN-a
-Multi component, impure IFN-a preps induce regression of tumours in breast cancer, lymphoma, multiple myleloma
- delay reoccurrence if tumours after surgery for osteo sarcoma
First recombinant interferon clinical studies
IFN-a2a properties
Anti- tumour
Anti-viral
Immunomodulatory
rhlFN-a2a / a2b Approved for:
-hairy cell leukaemia
-90% patients
IFN-a2b Intron A
Schering Plough, first approved 1986
Hairy cell leukaemia
Now up to 16 uses
Produced by E.coli (KMAC-43)
Contains phosphate buffer, glycine & human albumin
Dose: 3,5,10,18,25,59 million IU/vial
Treats HEP B & C
Modified INF-as examples
PEGlyated interferons: eg PEG Intron A, ViraferonPeg
Synthetic Interferons: eg Infergen
viraferonPeg
PEGlyated INF-a2b, differs from human by covalent attached PEG
Marketed by Schering Plough
Treats Hep C in adults
Prolonged plasma half life (13-25 hours)
Infergen IFN-a2b
Engineered & approved for Hep C
AA sequence reflects most most frequent as rescue in native interferon
Medical use IFN-b
Treat relapsing-remitting multiple sclerosis (damage of myelin sheath) (20-40 year old)
IFN-b inhibits IFN-a & IFN-y: mediates down regulation of pro inflammatory response
IFN-b approved drugs
Betaferon
Betaseron
Avonex
Rebif
Reduce frequency of relapse by 30%
Medical use IFN-y
Treat chronic granulomatous disease (CGD)
Patients can’t ingest or destroy bacteria or Protozoa = repeat infections
