243
response and possess redundant and pleiotropic effect. Cytokines IL-1 (α and β) and
TNF-α are involved in acute inflammation. Cytokines that mediate chronic inflammation are classified as follows: (a) those mediating humoral responses, such as
IL-4, IL-5, IL-6, IL-7, and IL-13; and (b) those mediating cellular responses, such
as IL-1, IL-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, interferons, transforming growth
factor α, and tumor necrosis factor α and β (Cook 2004; Feghali and Wright 1997).
IL-1 can significantly contribute to both acute and chronic inflammation. The activation of cytokine occurs by binding to the respective receptors on the surface of
target cells, which would induce a cascade of signaling events comprising the alteration at the gene level triggering the production and release of cytokines. Cytokines
exhibit autocrine, paracrine, and endocrine mode of actions. Certain subsets of cytokines possess immunomodulatory action as well by regulating T lymphocytes and
macrophages. Some cytokines can in turn inhibit or activate other cytokines.
Cytokines produced by leukocytes are interleukins, and so far about 25 of them have
been identified. Certain cytokines influence the generation of subpopulations of
helper T cells TH1 and TH2. Cytokine overproduction and activation has been
found to associate with a number of pathological manifestations. The high concentrations of TNF-α secreted by mast cells may contribute to shock in systemic anaphylaxis. TNF-α and IL-1 are found to be overproduced in response to bacterial
endotoxins and superantigens and trigger septic shock. Their activity is implicated
in many lymphoid and myeloid cancers as well as in autoimmune diseases and
diabetes.
Cytokines possess potential immune response-regulating activity and are mainly
synthesized by immune cells. They regulate immunity by directly influencing synthesis/differentiation of different subsets of T lymphocytes and activation of a variety of immune cells such as macrophages, cytotoxic T cells, and NK cells to
eliminate intracellular pathogens (Handa and Kowdley 2013; Jang et al. 2006).
They also enhance humoral immunity by activating TH2 cells, stimulating the generation of immunoglobulin isotypes, and augmenting IgE-mediated immune
responses. Interleukins (IL), a prominent subclass of cytokines, are bestowed with a
potential role in immune cell functional regulation. IL-1 enhances lymphocyte function and inflammatory response. IL-2 activates T cells and NK cells, IL-5 and IL-6
regulate T-cell synthesis and B-cell proliferation, and macrophage activation. IL-10
stimulates mast cell replication but negatively regulate cellular immune response.
Molecular mass of all types of cytokines falls below 30 kDa. Irrespective of the
variations in the amino acid sequences of these family members, all possess a similar degree of α-helical structure and little or no β sheet structure. The molecules
share a similar polypeptide fold, with four α-helical regions in which each pair of
helices run parallel to one another and are connected by loops (Rickert et al. 2005;
Trivella et al. 2010). Activation of cytokine is mediated via binding with the respective receptors expressed by many types of cells. Biochemical characterization of
cytokine receptors revealed the existence of five structurally diverse families of
receptors such as immunoglobulin superfamily receptors, class I cytokine receptor
family, class II cytokine receptor family, TNF receptor family, and chemokine
receptor family. Class I cytokine receptor family consists of cytokine-binding
10 Anti-inflammatory Molecules: Immune System Mediators
response and possess redundant and pleiotropic effect. Cytokines IL-1 (α and β) and
TNF-α are involved in acute inflammation. Cytokines that mediate chronic inflammation are classified as follows: (a) those mediating humoral responses, such as
IL-4, IL-5, IL-6, IL-7, and IL-13; and (b) those mediating cellular responses, such
as IL-1, IL-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, interferons, transforming growth
factor α, and tumor necrosis factor α and β (Cook 2004; Feghali and Wright 1997).
IL-1 can significantly contribute to both acute and chronic inflammation. The activation of cytokine occurs by binding to the respective receptors on the surface of
target cells, which would induce a cascade of signaling events comprising the alteration at the gene level triggering the production and release of cytokines. Cytokines
exhibit autocrine, paracrine, and endocrine mode of actions. Certain subsets of cytokines possess immunomodulatory action as well by regulating T lymphocytes and
macrophages. Some cytokines can in turn inhibit or activate other cytokines.
Cytokines produced by leukocytes are interleukins, and so far about 25 of them have
been identified. Certain cytokines influence the generation of subpopulations of
helper T cells TH1 and TH2. Cytokine overproduction and activation has been
found to associate with a number of pathological manifestations. The high concentrations of TNF-α secreted by mast cells may contribute to shock in systemic anaphylaxis. TNF-α and IL-1 are found to be overproduced in response to bacterial
endotoxins and superantigens and trigger septic shock. Their activity is implicated
in many lymphoid and myeloid cancers as well as in autoimmune diseases and
diabetes.
Cytokines possess potential immune response-regulating activity and are mainly
synthesized by immune cells. They regulate immunity by directly influencing synthesis/differentiation of different subsets of T lymphocytes and activation of a variety of immune cells such as macrophages, cytotoxic T cells, and NK cells to
eliminate intracellular pathogens (Handa and Kowdley 2013; Jang et al. 2006).
They also enhance humoral immunity by activating TH2 cells, stimulating the generation of immunoglobulin isotypes, and augmenting IgE-mediated immune
responses. Interleukins (IL), a prominent subclass of cytokines, are bestowed with a
potential role in immune cell functional regulation. IL-1 enhances lymphocyte function and inflammatory response. IL-2 activates T cells and NK cells, IL-5 and IL-6
regulate T-cell synthesis and B-cell proliferation, and macrophage activation. IL-10
stimulates mast cell replication but negatively regulate cellular immune response.
Molecular mass of all types of cytokines falls below 30 kDa. Irrespective of the
variations in the amino acid sequences of these family members, all possess a similar degree of α-helical structure and little or no β sheet structure. The molecules
share a similar polypeptide fold, with four α-helical regions in which each pair of
helices run parallel to one another and are connected by loops (Rickert et al. 2005;
Trivella et al. 2010). Activation of cytokine is mediated via binding with the respective receptors expressed by many types of cells. Biochemical characterization of
cytokine receptors revealed the existence of five structurally diverse families of
receptors such as immunoglobulin superfamily receptors, class I cytokine receptor
family, class II cytokine receptor family, TNF receptor family, and chemokine
receptor family. Class I cytokine receptor family consists of cytokine-binding
10 Anti-inflammatory Molecules: Immune System Mediators