CYTOKINES
SECRETED BY MACROPHAGES
Cytokines are
small proteins which allow cells of the immune system to communicate
with one another via cytokine receptors expressed at the cell
surface.
Macrophages secrete
the following cytokines under different conditions:
TNFalpha
- Tumour Necrosis Factor
alpha is made by many other cells as well as macrophages, which
are major sources, especially after priming by Interferon gamma.
- TNFa initiates
a cascade of cytokines which mediate an inflammatory response.
- TNFa effects
are mediated through two types of receptor, a 75kDa TNFR-a receptor and a 55kDa TNFR-b receptor.
- TNFa regulates
the expression of many genes in many cell types important for
the host response to infection.
IL-1beta
- Interleukin-1b is a pro-inflammatory cytokine which is secreted
by macrophages activated by a number of stimuli including TNFa, bacterial endotoxin and IL-1b itself.
- IL-1b exerts
its effects on many different cell types locally at the site
of production and systemically (at a distance).
Interferon
alpha/beta
Macrophages, and
many other cells produce these Type I interferons which act as
immunomodulatory, as well as antiviral cytokines.
- Distinct receptor from
interferon gamma, mediates overlapping or competing effects on
macrophages.
- Cellular signalling pathways
involve Jak/Stats, and other pathways.
IL-6
- Interleukin 6 is a pro-inflammatory cytokine and
is produced in response to infection and tissue injury. IL-6
exerts its effects on multiple cell types and can act systemically.
- IL-6 stimulates liver
secretion of acute phase proteins
- IL-6 stimulates B-lymphocytes
to produce antibodies
- IL-6 in concert with IL-1
causes T-cell activation
IL-10
- Interleukin 10 is an immunoregulatory cytokine which
can exert a wide range of different effects on different cell
types.
- IL-10 suppresses IL-2
and IFN g production by TH1 T-cells.
- IL-10 is a potent modulator
of monocyte/macrophage function down-regulating proinflammatory
cytokine production, and the respiratory burst.
IL-12
- Interleukin-12 is a heterodimer
consisting of a p35 and a p40 subunit. Both subunits are required
for receptor binding and biological activity.
- IL-12 stimulates growth
of activated Natural Killer (NK) cells, CD8+ and CD4+ T- cells.
- IL-12 increases NK and
T-cell g-IFN production which shiftsT-cell
differentiation towards a Th1-type response.
- IL-12 increases NK production
of TNFa which can act synergistically
with g-IFN.
- IL-12 suppressses IL-4
induced IgE production.
IL-18
- Interferon gamma inducing
cytokine synergises with IL-12.
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