|Cytokine & Chemokine Technical Article
The immune system recognizes the presence of pathogens by several proteins
that bind to molecules secreted by the pathogen or carried on their surface. The cells responsible for these immune
responses include the B-Cells, T-Cells, macrophages, neutrophils, basophils, eosinophils, endothelial cells, or mast cells
(Ref.1). These cells have distinct roles in the immune system, and communicate with other immune cells by cytokines, which
control proliferation, differentiation and function of cells of the immune system. Furthermore, they are involved in
processes of inflammation and in the neuronal, haematopoietic and embryonal development of an organism.
Unlike hormones, cytokines are not stored in glands as preformed molecules,
but are rapidly synthesized and secreted by different cells mostly after stimulation. Cytokines are pleiotropic in their
biological activities and play pivotal roles in a variety of responses, including the immune response, hematopoiesis,
neurogenesis, embryogenesis, and oncogenesis. They frequently affect the action of other cytokines in an additive,
synergistic or antagonistic manner.
Cytokines have been classified on the basis of their biological
responses into pro- or anti-inflammatory cytokines, depending on their effects on immunocytes (Ref.2). Cytokines act in
networks or cascades. Major cytokines include the ILs (Interleukins), Growth Hormone, IFN (Interferons) and TNFs
(Tumor Necrosis Factors-Alpha and Beta). Many of the cytokines act locally like autocrine hormones and their targets
are cells of the same or similar type as the cytokine-producing cell. A characteristic that significantly differentiates
some of the cytokines from hormones is the coupling of their activity to cell-cell interactions. The function of some
cytokines such IL-1, IL-2, IL-4, IL-5, IL-6 and IL-10 is closely associated with the interactions between B-Cells and
T-Cells (Ref.3). IL-1 activates Antigen presenting cell and CD4+ lymphocytes; affect the differentiation of the B-Cells
and T-Cells and other immunocompetent cells and takes part in the regulation of productions of other cytokines and
GMCSF (Granulocyte-Macrophage Colony-Stimulating Factor) (Ref.6). IL-2 stimulates the proliferation and activation of
B-Cells and T-Cells. IL-4 plays a role in the differentiation of TH2 (T Helper Type-2), in allergic responses, and in the
switching of antibody types. IL-5 stimulates the production and maturation of eosinophils during inflammation. IL-8 acts
as a chemotactic factor that attracts neutrophils, basophils and T-Cells to sites of inflammation. IL-12 is a critical
linker between the innate immunity and adaptive immunity, capable of TH1 (T Helper Type-1) differentiation and IFN-Gamma
release by T-Cells and NK cells (Ref.4). IL-10 acts to repress secretion of pro-inflammatory cytokines. IL-3 is a poly
potent activator of the hemopoietic cells. It stimulates NK-Cells and acts as a synergist with IL-4 during the induction
of CD4+ lymphocyte activation process. IL-7 is known as the growth factor of the immature B-Cells and T-Cells. It induces
apoptosis of tumor cells and causes differentiation of cells from a subgroup of acute myeloblastic leukemia. IL-9
stimulates the excretion of IL-2, IL-4, IL-6, IL-11, and takes part in a stimulation of cytotoxicity of T-killers and
NK-Cells, inducing apoptosis. IL-11 is a pro-inflammative factor, which regulates the functions of B-Cells and T-Cells.
It also takes part in the induction of various killer cells' activities and acts as an autocrine factor for the
proliferation of megacaryocytes. IL-13 is very sensitive to the monocytes and B-Cells. IL-13 does not act on T-Cells
but inhibits the proliferation of leukemic pro-B-Cells. IL-14 is a BCGF (B-Cell Growth Factor) and the hyper production
of this interleukin enables the progression of NHL-B (B-cell type non Hodgkin's lymphoma). IL-15, in the biological
properties, is very much analogous to IL-2 and increases the antitumor activities of T-killers and NK-Cells, and the
production of cytokines CD4+ lymphocytes. IL-17 is principally produced by CD4+ T-Cells, which induces granulopoiesis
via GMCSF. It takes part in the regulation of many cytokines and can reinforce the antibody dependant tumor cell
destructions. IL-18 acts as a synergist with IL-12 in some of their effects, especially in the induction of IFN-Gamma
production and inhibition of angiogenesis. IL-19 is produced mainly by monocytes and in its biological function is similar
to IL-10. It is stimulated by GMCSF and regulates the functions of macrophages, and also suppresses the activities of TH1
and TH2. IL-21 executes an important role in the regulation of haematopoiesis and immune response. It promotes a high
production of T-Cells, fast growth and maturation of NK-Cells and B-Cells population. IL-22 is produced by activated
T-Cells in an acute stage of inflammation. In its bioactivities, it is similar to IL-10, but does not prohibit the
production of pro-inflammatory cytokines through monocytes (Ref.1). The complex interplay of these different cytokine
functions with immune cells is essential for correct immune function.
In addition to the above cytokines, the release of other inflammatory
cytokines, particularly TNFs (TNF-Alpha and TNF-Beta) from mast cells and the associated recruitment of neutrophils are
an important component of the protective action of mast cells against infestation. The secretion of TNF-Alpha and TNF-Beta
by TH1 cells activates macrophages, inhibits apoptosis of neutrophils and eosinophils, and induces vascular endothelial
cells at the sites of infection to change the adhesion molecules they express so phagocytes circulating in the blood can
bind to them (Ref.6). IFN-Alpha, IFN-Beta and IFN-Gamma are produced in the area of infection during the early phase of
immune response. IFN-Alpha and IFN-Beta induce proliferation of NK-Cells and stimulate innate and adaptive immune responses
that are specifically targeted to virus infections. Upon activation NK cells release IFN-Gamma, which activates macrophages
to secrete cytokines that help to activate macrophages to secrete cytokines that help to activate T-Cells and promote the
initiation of T-Cell responses.
Cytokines play an important role in the communication between cells of
multicellular organisms. As intercellular mediators, they regulate survival, growth, differentiation and effector
functions of cells. Besides their pleiotropic effects, cytokine actions are often redundant and they exert their actions,
which can be auto-, para- or endocrine, via specific cell-surface receptors on their target cells (Ref.2). They are key
players in the regulation of the immune response, particularly during infections, inflammatory joint, kidney, vessel and
bowel diseases, or neurological and endocrinological autoimmune diseases (Ref.5).
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Immune System, Immune Responses, Immune Cells, Immunocytes, Cytokines,
IL, Interleukins, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-17,
IL-18, IL-19, IL-21, IL-22, Erythropoietin, Growth Hormone, IFN, IFN-Gamma, Interferons, TNF, Tumor Necrosis Factor, CD4+
Lymphocytes, Th2, T Helper Type 2, Th1, T Helper Type 1, Pathogen, B-Cells, T-Cells, Lymphocytes, Granular Lymphocytes,
NK-Cells, Natural Killer Cells, Proliferation, Differentiation, Inflammation, Haematopoiesis, Haematopoietic,
Embryonal Development, Viral Infection, Immunocompetent, Hemopoietic Cells, Apoptosis, Tumor Cells, Acute Myeloblastic
Leukemia, Cytotoxicity, Granulopoiesis, Angiogenesis, Endocrinological Autoimmune Diseases, Neurogenesis, Embryogenesis,
Oncogenesis, Infestation, Adhesion.
Macrophages, Neutrophils, Basophils, Eosinophils, Endothelial Cells, Mast
Cells, Pleiotropic Proteins, Cell-Cell Communication, Pro- Inflammatory Cytokines, Anti-Inflammatory Cytokines, Autocrine
Hormones, Antigen Presenting Cell, GMCSF, Granulocyte-Macrophage Colony Stimulating Factor, Chemotactic Factor, Innate
Immunity, Adaptive Immunity, Growth Factor, T-Killers, Antibody, Monocytes
Cytokines, Cell Signaling, Hematopoiesis, Immunology