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On several bases, cytokines may be classified [Table 2]. Mostly, cytokines are produced and act
[10]
depending on their (1) cell of origin; (2) spectrum of locally. A minority enter the systemic circulation
activity; (3) the category of activity they influence; in biologically relevant amounts and a few have an
(4) the cells that are their targets; or (5) on specific important physiological role there. However, their
[7]
features of their ligand-receptor interaction, “endocrine” role is subtly different from that of
although the nomenclature is somewhat arbitrary, classical endocrine hormones. Whereas the purpose
[8]
having arisen in different branches of biology [Table 1]. of endocrine hormones is to ensure the efficient
Extensive genetic polymorphisms have also been function of normal tissues and the whole organism,
described, which in many cases appear to play an cytokines with a physiological role in the circulation
important part in their level of expression and have are concerned with restoring normal function to the
been linked to a variety of diseases, as a variety tissue in which they were produced. Indeed, when
[6]
of experiments has shown that either excessive or tissues are severely challenged, and larger amounts
insufficient production of cytokines may contribute of cytokines do enter the circulation, they may be
significantly to the pathophysiology of a range of responsible for upsetting systemic homeostasis,
diseases including hepatic diseases. [9] inducing fever, sickness behavior, cachexia and
[2]
a variety of endocrine hormone imbalances.
[11]
GENERAL PROPERTIES OF CYTOKINES Individual cytokine either in tissues or in the
circulation may exhibit a range of activities and many
Cytokines can be produced by virtually every of these overlap with activities of other cytokines. [12]
nucleated cell type in response to injurious stimuli
STRUCTURAL ORGANIZATION OF THE LIVER AND
Table 1: Important classes of cytokines (Ikram et al. ) CYTOKINES POTENTIAL IN ITS DAMAGE
[8]
Cytokines classes
Growth factors The liver consists of several cell types that under
Haemopoietic growth factors; granulocyte-colony stimulating normal circumstances produce only minimal levels of
factor; granulocyte macrophage-colony stimulating factor; cytokines. When liver cells, particularly immune cells
erythropoietin; thrombopoietin; stem cell factor or c-kit ligand
called Kupffer cells (KC), become activated cytokine
Epidermal growth factor production increases dramatically; therefore, if the
Platelet derived growth factor liver has been damaged, cytokines mediate the
regeneration of liver tissue. Also, KC can be activated
Transforming growth factor β
by diseases caused by microorganisms or substances
Fibroblast growth factor
(i.e. pathogens). In this case, cytokines produced and
Insulin like growth factor released by the KC induce an inflammatory response
Nerve growth factor in the liver (hepatitis), which is required to start the
ILs
healing process. However, if the inflammation does
IL-1 to IL-18, etc. not subside after a short time, persistent production
IFNs
of these same cytokines may lead to formation of
IFN-α fibrosis and cirrhosis. Thus, cytokine production can
IFN-β have both beneficial and harmful effects, depending
IFN-γ on the amount and duration of cytokine release.
Miscellaneous The architecture and cellular composition of the
Tumour necrosis factor, etc. healthy liver in numbers indicating the estimated
IL: interleukin; IFN: interferon frequency of each population relative to the total
Table 2: Cytokine properties (Oppenheim [10] ) number of parenchymal and nonparenchymal
Cytokine properties cells in the liver is shown in Figures 1 and 2. This
Low molecular weight protein/glycoproteins discontinuous structure allows contact between
Almost all cells produce some cytokines hepatocytes and lymphocytes. The contact can
either be produced through hepatocyte microvilli
A single cytokine may be produced by many cell types
protruding into the lumen or by lymphocyte
Cytokine expression is usually induced, not constitutive
pseudopod extensions penetrating into the space of
Have a pleiotropy: one cytokine may exhibit many biological Disse. The space of Disse contains hepatic stellate
activities
cells (HSCs, fat storing). KC reside within the liver
Have redundancy: several cytokines may share the same/similar
activities sinusoidal vascular space, predominantly in the
132 Hepatoma Research | Volume 2 | June 1, 2016