Interferon

Dr. Waqas Nawaz
PMAS arid agriculture university rawalpindi

1. SUBMITTED TO:
Dr.Saif ur Rehman
SUBMITTED BY:
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2. Natural
Interferons
Man Made
Interferons
(Recombinant)

3. Interferons play an important role in the first
line of defense against viral infections
Interferons are part of the non-specific immune
system
Interferons are made by cells in response to an
appropriate stimulus

4. alpha (leukocyte interferon)
produced by virus infected leukocytes
beta (fibroblast interferon)
produced by virus infected fibroblasts or epithelial
cells
gamma (immune interferon)
produced by certain activated T cells & NK cells

5. virus
cells
(Other stimuli:
exogenous ds RNA,
LPS, bacterial
components)

6. virus
interferon

7. virus
Inhibitor
y
proteins
No replication

10. IFN alpha and beta
induction of inhibitory protein synthesis
IFN gamma
inc class II MHC molecules of APC
Inc ability of macrophages to resist viral infx and kill
other cells if infected
All IFN
inc class I MHC molecules
inc activity of NK cells

11. block interferon binding to cells
inhibit action of interferon-induced protein
kinase
inhibit NK function
interfere with cell surface expression MHC
block complement activation
prevent apoptosis in host cell

12. alpha
Hepatitis B & C, Hairy cell leukemia, Chronic
myeloid leukemia, multiple myeloma, low grade
lymphomas, Kaposi’s Sarcoma, Melanoma
beta
Multiple Sclerosis, (Ulcerative colitis)

13. gamma
Chronic granulomatous disease, Chronic Myeloid
Leukemia, Renal cell Carcinoma

14. Actimmune
Alferon
Avonex
Betaserone
Infergen
Intron
Wellferon, etc

15. HCV is leading cause of liver disease
4 million Americans have been exposed
approx 3 million are infected
HCV infection leads to decompensated
cirrhosis and hepatocellular carcinoma
HCV-related cirrhosis is the most common
reason for OLT in the US
NIH Consensus Development Conference Statement 2002

17. Consensus Statement in 2002
treatment eligible patients
IVD users, consume alcohol, comorbidities (depression,
HIV coinfections)
pegylated interferon with ribiviran better than
peginterferon monotherapy or standard interferon-
ribivarin

19. Monotherapy
standard interferon 3 Million units inj tiw (Low
Sustained virologic response)
Combination therapy
standard interferon with ribivarin
pegylated interferon with ribivarin

20. Limitations
monotherapy not very effective
cumbersome dosing (TIW)
multiple side effects

21. Flu-like symptoms
Headache
Nausea, vomiting, diarrhea
Depression, irritability, anxiety
Injection site reactions, partial alopecia
Hematologic abnormalities
Autoimmune disorders
(Hepatitis C Data)

22. Depression (77% Manns et al, Lancet 2001)
NIH consensus - “monitor patients for depression
and prescribe antidepressants when necessary”
Hematologic abnormalities
neutropenia and thrombocytopenia
treatment options include decreasing dose or giving
hematopoietic growth factors

23. HCV is an ideal setting for peginterferon
polyethylene glycol (PEG):interferon
Pegylation was developed to overcome
disadvantages of standard interferon
shields IFN from enzymatic degradation thus lowers
systemic clearance
allows less frequent dosing
achieve higher/sustained serum [interferon]

24. 0%
10%
20%
30%
40%
50%
60%
Pega2a IFN a2b+RBV Pega2aRBV
monotherapy
IFN+RBV
Peg+RBV
P=<0.001
29%
44%
56%

25. peginterferon alfa-2b
linear molecule
weight 12 kDa
peginterferon alfa-2a
larger, branched molecule
weight 40 kDa

28. Peg alfa-2bPeg alfa-2a
Volume of
distribution
20 L 8 L
Absorption half-life
(h)
4.6 50
Mean elimination
half-life (h)
40 80

29. Once weekly dosing
alfa 2b
weight based dosing (1-1.5 mcg/kg/week)
high volume of distribution
kidney, heart, liver and throughout the bloodstream
alfa 2a
fixed dose at 180 mcg/week
low volume of distribution

30. Interferons are important in the nonspecific
immune response
Interferons are effective in the treatment of
patients with chronic hepatitis
Pegylated interferons are superior therapies for
patients with HCV
Side effects should be monitored closely