Cytokines are a group of low molecular weight, soluble proteins
that are made by cells in the immune system and which effect and regulate
the activity of other cells.
(Cytokines produced by lymphocytes
are called lymphokines, those made by monocytes can be called monokines.
Many cytokines are also known as interleukins).
Cytokines that regulate the
chemotaxis of immune cells are referred to as chemokines.
Cytokines work in concert
with other cytokines producing additive, synergistic or antagonistic effects.
In order
for a cytokine to have an effect on a "target" cell, the target
cell must have a receptor for the cytokine. (The expression of a receptor
by a cell can be dynamic, i.e., may be up-regulated or down-regulated
The target
cell may either be autocrine
or paracrine
Some
cytokine receptors have certain chains in common Ð this leads to some
overlapping effects between different cytokines.
Types of cytokines:
Cytokines
that regulate the immune response
Many
of these are made by CD4(+) T-cells. These cells are also under
the "spell" of other cells:
Remember
IL-12 from dendritic cells can drive TH0 cells to become
TH1 cells. Alternatively, IL-4 from mast cells (or
other T cells) will influence TH0 cells to become TH2
cells.
Cytokines
that regulate innate immunity and inflammation
Many
of these are made by immune cells that have been triggered by microbial
pathogens via TLR's.
Endogenous
pyrogen - a group of cytokines that cause fever responses: IL-1,
IL-6 and TNFa -- in addition to resetting the thermostat in
the hypothalamus, these cytokines mobilize energy via fat and protein
breakdown to allow for increased body temp.
This
group of cytokines also causes the synthesis and release of acute
phase proteins by the liver. These acute phase proteins
include C-reactive protein and mannan-binding lectin,
soluble "pattern recognition" molecules that opsonize and
activate complement. (Kind of a "primitive" antibody)
This
group also causes the number of circulating neutrophils to increase.
They also cause dendritic cells to begin migrating to the spleen and
lymph nodes
These
cytokines are also referred to as proinflammatory -when local
levels are high, they can cause increased vascular permeability and
promote the adhesion of neutrophils to the vascular endothelium of
the area.
Cytokines
that affect leukocyte movement -The Chemokines
These
are also generally considered to be pro-inflammatory.
Cytokines
that stimulate Hematopoiesis
The role of Cytokines
in Disease
Toxic Shock
Syndrome Ð Extremely large numbers of TH cells become activated
by superantigens leading to extremely high levels of IL2, IL-1 and
TNF-a. Severe systemic reactions lead to shock
and sometimes death.
Bacterial
septic shock (endotoxin shock) - Lipopolysaccharide (endotoxin) recognized
by TLR's cause macrophages to overproduce IL-1 and TNF-a.
Severe systemic reactions lead to shock and sometimes death.
Some cancers
produce the cytokines they need to promote their own growth
Adult
onset T-cell leukemia - IL-2
Myeloma
- IL-6
Hodgkin's
lymphoma - IL-5
Allergy
and autoimmunity
Allergies
- faulty TH2 response? - too much IL-4 and IL-13
SLE -
too much IL-10?
Promising
therapies?
Use soluble
TNFa receptors to treat rheumatoid arthritis - diminishes inflammation
in most patients.