Basic Science applied to medicine

1. CYTOKINES
Role in Acute Inflammation

2. Overview
• What are cytokines
• General properties of Cytokines
• Roles of various cytokines in inflammation
• Interleukins
• Chemokines
• Applied aspects

3. Cytokines
• combination of two Greek words –
• "cyto" meaning cell and "kinos" meaning movement.

4. Cytokines are low molecular weight regulatory proteins or glyc
Secreted by white blood cells and various other cells in the bod
response to a number of stimuli.
Mainly by activated lymphocytes, macrophages, and den
but also endothelial, epithelial, and connective tissue cel
Mediate INFLAMMATORYand IMMUNE reactions

5. Cytokine is actually a general term
Other names
Interleukins lymphokines Monokines Chemokines
Produced by
one leukocyte
ad act on other
leukocyte
Produced by
Lymphocytes
Produced by
Monocytes
Cytokines which
are having
chemotactic
activities
Interferons
Involved in
antiviral
responses
Colony stimulating
factors
Supports the
growth of blood
cells

6. Actions: general Properties
ENDOCRINE ACTION
Circulation Distant ce

7. PARACRINE ACTION
Nearby cell

8. AUTOCRINE ACTION

9. Other Properties Exhibited by cytokines
Pleiotrophic
Redundancy
Cascade
Induction
Synergy
Antagonism
Different cell types can secrete the same cytokin
single cytokine can act on several different cell
Similar functions can be stimulated by different
cytokines.
One cytokine stimulates its target cells to make
additional cytokines.
Combination of cytokines produce a combined e
greater than the sum of their separate effects.
Two cytokines can have opposite action

11. • Mediate the leukocyte cross-talk (hence the name)
• Up to 38 ILs have been so far identified, numbered according t
order of discovery
• Involved in the pathogenesis of human inflammatory/autoimm
diseases
INTERLEUKINS

12. • The interleukins and other cytokines which have a significant
Acute inflammation are
• IL-1
• IL-6
• IL-17
• TNF-alpha
• Chemokines

13. • Two most important cells which are the sources of most of the
cytokines are
• MACROPHAGES & T LYMPHOCYTES
INTERLEUKIN-1
INTERLEUKIN-6
TNF-α
INTERLEUKIN-17
TNF-β

14. INTERLEUKIN-1 INTERLEUKIN-6 INTERLEUKIN-17
Macrophages ,
Fibroblasts, endothelial
cells & few epithelial cells
Macrophages, Fibroblasts
endothelial cells & few
epithelial cells
T Lymphocytes
Stimulates expression of
endothelial adhesion
molecules
Emigration of neutrophils &
macrophages
Secretion of other cytokines
Fever
Systemic Response:
Production of
Acute Phase Reactants
from liver
Particularly important in
inducing B-Cells to
differentiate into antibody
producing Cells (Plasma
Cells)
Recruitment of
neutrophils and
monocytes
Secretion of other
cytokines like IL-6, G-C
GM-CSF, IL-1β, TNF-α
chemokines

15. TUMOR NECROSIS FACTOR -α
Macrophages cells, Fibroblasts endothelial
cells & few epithelial cells
Stimulates expression of endothelial adhesion
molecules
Emigration of neutrophils & macrophages
Secretion of other cytokines
Fever
Regulates energy balance by promoting lipid
and protein catabolism and by suppressing
appetite
TUMOR NECROSIS FACTOR
B & T lymphocytes only
Cellular cytotoxicity
Development of spleen and lymph no
Not much role in acute inflammation

16. CHEMOKINES
Macrophages cells &endothelial cells
Family of Small 8-10kD proteins
Act as chemoattractant for
leukocytes
They Bind to 7 transmembrane G
protein coupled receptors
They direct the movement of
circulating leucocytes to the site of
inflammation and injury.

17. C chemokines
CC chemokines
CXC chemokines CX3C chemokines
Adapted from ©Kohid
TYPES

18. CC chemokines
.
CC chemokines induce the migration
monocytes
Also NK cells and dendritic cells.
Examples:
Monocyte chemoattractant
protein-1 (MCP-1 or CCL2)
Inducesmonocytes to leavebloodstrea
and entersthe tissue to become
macrophages
CCL5 ( RANTES)Regulated on
Activation, Normal TCell
Expressed and Secreted
Attracts cells such as T cells, eosinop
and basophils

19. The two N-terminal cysteines are
separated by an amino acid,
represented in this name with an "
CXC chemokines induce the
migration of Neutrophils&
LymphocytesExamples:
Interleukin-8 (IL-8) Induce the migration of Neutrophi
CXCL13
Induce the migration of
Lymphocytes
CXC chemokines

20. C chemokines
Has only two cysteines
Examples:
XCL1 lymphotactin-α and XCL2
lymphotactin-β.
Induces migration of
lymphocytes

21. CX3C chemokines
Examples:
Fractalkine(or CX3CL1)
Both a chemoattractant
Chemotactic for monocytes,
natural killer (NK) cells, an
cells
and as an adhesion molecu

22. Apart from their role in inflammation some chemokines orga
various cell types in different anatomic regions of the
tissues/organs.
Such as T and B lymphocytes in discrete areas of the spleen
lymph nodes
These are called homeostatic chemokines.

23. ROLE OF OTHER CYTOKINES
IL12, IL17 & IFN-γare involved in chronic inflammation
Interferons Also Involved in antiviral responses
Colony stimulating
factors
Supports the growth of blood cells
eg.IL7,GM-CSF etc.

24. APPLIED ASPECTS
IL-6 receptor antagonists are
used in the treatment of
rheumatoid arthritis
IL-17 antagonists are very
effective in psoriasis and
other inflammatory diseases.
Inhibiting cytokines can prevent
some harmful effects of
inflammation and immune
reaction
Inflammation is a double
edged sword!
Interferons used in the treatm
of viral diseases
GM-CSF increases white cell
count, used after bone marrow
transplantation, Chemotherap
induced neutropenias