Easy notes cytokines

1. CYTOKINES
SUMIT KUMAR

2. Cytokines
Cyto- cell kines – movement(greek)
A group of low molecular weight soluble
polypeptides or proteins which are
secreted by activated immunocytes or some
matrix cells and possess high activity and
various functions (mediate & regulate
immune responses and inflammatory
reactions).

3. Classification of cytokines
Interleukin(IL)
Interferon (IFN)
Tumor necrosis factor(TNF)
Chemokines(CK)
Colony stimulating factor(CSF)
Transforming growth factor(TGF)

4. Nomenclature
Interleukins - that act as mediators between leukocytes. The vast
majority of these are produced by T-helper cells.
Lymphokines - produced by lymphocytes.
Monokines - produced exclusively by monocytes.
Interferons - involved in antiviral responses.
Colony Stimulating Factors - support the growth of cells in semi-
solid media.
Chemokines - mediate chemoattraction (chemotaxis) between
cells.

5. PROPERTIES
1. Mostly low molecular weight small
polypeptides or glycoprotein(8~80 KD), and
most of them are monomer.

6. 2.Natural cytokines are secreted by activated cells such as
activated immune cells, matrix cells and some tumor cells.
Mostly Cytokines are not stored inside cells (exceptions
are, for example TGF-β and PDGF which are stored in
platelets.)
3.Effects of cytokines :
Pleiotropism refers to the ability of one cytokine having
multiple effects on diverse cell types
Redundancy refers to the property of multiple cytokines
having the same or overlapping functional effects
Synergy refers to the property of two or more cytokines
having greater than additive effects.
Antagonism refers to the ability of one cytokine inhibiting
the action of another.

8. 4.Cytokines initiate their actions by binding to
specific membrane receptors on target cells.
5.Only small quantities of cytokines are needed
to occupy receptors and elicit biologic effects.
6.Cytokines act on target cells by the 3 way :
Autocrine - Cytokine binds to receptor on same
cell that secreted it.
Paracrine -Cytokine binds to receptors on near
by cell.
Endocrine - Cytokine binds cells in distant parts
of the body after being carried in blood or tissue
fluids.

9. Distance
autocrine
endocrine
Blood circulation
paracrine Nearby
self

10. Cytokine -mediated effects
Cell growth
Cell differentiation
Cell death
Induce non-responsiveness to other
cytokines/cells
Induce responsiveness to other
cytokines/cells
Induce secretion of other Cytokines(Cascade Effect)
Th

11. Proinflammatory Cytokines TNF, IL-1, IL-6 , Chemokines (mostly)
Anti-inflammatory Cytokines IL-4,IL-10 ,IL-13, TGF-β, IL-1 ra
Antiviral Cytokines IFN-α,IFN-β,
Macrophages Activating Cytokines IFN-γ
B-cell Activating Cytokines IL-4, IL-5,IL-6, IL-21
T- Cell Activating Cytokines IFN-γ, IL-2, IL-4 , IL-12
Eosinophil And / Or Mast Cell Activating
Cytokines
IL-3, IL-4, IL-5, IL-13

12. Types of cells producing Cytokines
Fibroblasts
Reticulum Cells
Macrophages
T- Cells
Bone Marrow Stromal Cells
B – Cells
Neutrophils
Natural Killer Cells
Basophils
Eosinophils
Endothelial Cells
Kidney Cells
Liver Cells

13. Interleukins(IL)

14. Cytokines secreted by leukocytes that have
the ability to act as signal molecules
between different population of leukocytes.
Eg.IL-1 –IL22

15. Interferon (IFN)

16. A group of glycoproteins that produced by
human or animal cells following the infection of
virus and exposure to various inducing agents.
Types:
Type I- IFN-α , IFN-β, IFN- ω, bind to a specific
cell surface receptor complex known as the IFN
α receptor (IFNAR) that consists
of IFNAR1 and IFNAR2 chains.
Type II- IFN-γ, Binds to IFNGR that consists
of IFNGR1 and IFNGR2 chains
Type III- Signal through a receptor complex
consisting of IL10R2 (also called CRF2-4)
and IFNLR1 (also called CRF2-12).

18. Chemokines
(CK)

19. Cytokines which recruiting monocytes,
granulocytes and lymphocytes in blood to
the sites of inflammation & act through
G-PCR.
Types:
CXC chemokines(α subgroup):IL-8
(Acute inflammation)
CC chemokines(β subgroup):MCP-1,
RANTES (Chronic inflammation)
C chemokines(γ subgroup): Lymphotactin
CX3C chemokines(δ subgroup)
*C: cysteine; X: any amino acid

20. Tumor necrosis
factor (TNF)

21. Refers to a group of cytokines that can cause cell
death (apoptosis).
Types:
TNF- produced mainly by activated monocytes
and macrophages, implicated in tumor
regression, septic shock, and cachexia.
TNF- (lymphotoxin alpha, LT-α) is produced
mainly by activated Th0 and Th1, inhibited
by interleukin 10. Lymphotoxin-alpha (LT-alpha)
and lymphotoxin-beta (LT-beta), two related
cytokines produced by lymphocytes that are
cytotoxic for a wide range of tumor cells in vitro
and in vivo.

23. Colony-stimulating factors
(CSF)

24. Colony-stimulating factors (CSFs) are secreted
glycoproteins that bind to receptor proteins on the
surfaces of hemopoietic stem cells , stimulate
proliferation andor differentiation of pluripotent
hematopoietic stem cell and different progenitors
(Stimulate hematopoiesis )
Includes:
MCSF-Macrophage colony-stimulating factor
GMCSF-Granulocyte macrophage colony
stimulating factors.
GCSF-Granulocyte colony-stimulating factors
SCF-Stem cell factor
EPO-Erythropoietin
Multi-CSF (IL-3, IL-7)- growth of lymphocyte progenitor
cells.

26. Transforming growth factor
(TGF)

27. Transforming growth-factor are cytokines which
stimulate the growth of their target cells.
Include:
 Transforming growth factor-(TGF- )
 Epithelial growth factor(EGF)
 Vascular endothelial cell growth factor(VEGF)
 Fibroblastic growth factor(FGF)

28. Therapeutic Uses of Cytokines
1.Interferon(IFN) in treatment of viral diseases, cancer.
Eg. IFN-  treatment of condylomata acuminata (venereal or genital
warts), malignant melanoma, hairy cell leukemia and hepatitis B and C,
and other types of cancer including skin, kidney and bone cancers.
IFN-β- multiple sclerosis
IFN- -Chronic granulomatous disease in conjuction with other
antibacterial drugs
2.Cytokines are used to enhance T-cell activation in immunodeficiency
diseases, Eg. IL- 2, IFN-(Induction of Th 1 response),TNF-
3. GM-CSF & G-CSF) induces increase in white cell count, it is used:
a- To restore leukocytic count after cytotoxic chemotherapy induced
neutropenia
b- After bone marrow transplantation
C- To correct AIDS-associated leukopenia
Eg. G-CSF-Filgrastim, used to treat neutropenia in cancer patients.
GM-CSF-Sargramostim- used to treat neutropenia and fungal infections
in cancer patients.

29. 4.Erythropoietin (EPO)-In Treatment of anemia of chronic renal
disease , in cancer patients on chemotherapy
5. Interleukin 2 (IL2)- Used to treat cancer
Eg:Aldesleukin -treatment of renal cell carcinoma, metastatic
melanoma & non-Hodgkin’s lymphoma (NHL).
6.Anakinra-IL-1 receptor antagonist used in treatment of severely
active rheumatoid arthritis . It reduces inflammation, decreases bone
and cartilage damage.
7. Etanercept- TNF- receptor agonist, treatment of rheumatoid
arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis and
psoriatic arthritis
8. IL-11 stimulate Platelet production, used in treatment of
thrombocytopenia caused by myelosuppressive agents.

30. Thank you