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10.2.4 Leukotrienes
Leukotrienes (LTs) are a class of eicosanoids which have inflammatory and immunomodulatory actions by stimulating the infiltration of immune cells. LTs are synthesized by the oxidation of arachidonic acid by arachidate-5-lipoxygenase from
leukocytes. They have a prominent role in allergic hypersensitive reactions and
facilitate mucus production. Leukotrienes are activated by coupling with specific
receptors falling under G protein-coupled receptor families. Once activated, they
enhance leukocyte accumulation, phagocytosis, and microbicidal activity.
Leukotrienes facilitate immunomodulatory functions as well and regulate both
innate and adaptive immune responses. LTs with inflammatory functions are divided
into two classes, namely, LTB4, which carries hydroxyl moieties, and the cysteinyl
LTs (LTC4, LTD4, and LTE4), which carry a cysteine amino acid moiety. Leukotriene
B4 causes adhesion and chemotactic properties. It aids in superoxide generation in
neutrophils. The cysteinyl leukotrienes are potent bronchoconstrictors and promote
vascular permeability and mucus secretion. Thus, they are regarded as the principal
components playing pathophysiological role in immediate hypersensitivity reactions. Among these, LTB4 is considered as the most potential inflammatory mediator. Agents inhibiting the biosynthesis of leukotrienes, such as LOX inhibitors, act
as potential anti-inflammatory agents.
Chemically, leukotrienes are lipid molecules with hydroxyl or amino acid moieties. The presence of three conjugated double bonds is the common feature of
leukotrienes. Based on the affinity toward different types of leukotrienes, the receptors are categorized into LTB4 receptor and cysteinyl LT receptors (cysLT1 and
cysLT2). LTB4 receptors facilitate the binding of LTB4 and thereby facilitate leukocyte infiltration and promote release of cytokines and lysosomal enzymes from
immune cells. Two receptors for the cysLTs, termed type 1 and type 2 cysLT receptors, have been identified so far (Chagnon et al. 1985; Parker 1982). These receptors
are also extensively exploited as potential anti-inflammatory targets. LTD4 is the
preferred binding agonist of the cysLT1 receptor, and LTC4 is the preferred binding
partner of the cysLT2 receptor. This triggers bronchoconstriction, migration of
eosinophils into the airways, and mucus secretion. CysLTs and their receptors are
thus considered as the chief participants in asthmatic and allergic reactions.
10.2.5 Cytokines and Sub-families
These low-molecular-weight regulatory glycoproteins propagate many vital cellular
events like immune response modulation, hematopoiesis, and inflammation. They
are primarily secreted by various cells such as macrophages and T lymphocytes in
response to a variety of immunologic or nonimmunologic stimuli. Cytokines are
categorized on the basis of their biological response and effect on immunocytes and
comprise both pro- and anti-inflammatory cytokines. Major proinflammatory cytokines include lymphokines, interferon, monokines, interleukin, colony-stimulating
factor, and tumor necrosis factor (TNF) α and β. Cytokines regulate inflammatory
B.C. Bhavya and M. Haridas
10.2.4 Leukotrienes
Leukotrienes (LTs) are a class of eicosanoids which have inflammatory and immunomodulatory actions by stimulating the infiltration of immune cells. LTs are synthesized by the oxidation of arachidonic acid by arachidate-5-lipoxygenase from
leukocytes. They have a prominent role in allergic hypersensitive reactions and
facilitate mucus production. Leukotrienes are activated by coupling with specific
receptors falling under G protein-coupled receptor families. Once activated, they
enhance leukocyte accumulation, phagocytosis, and microbicidal activity.
Leukotrienes facilitate immunomodulatory functions as well and regulate both
innate and adaptive immune responses. LTs with inflammatory functions are divided
into two classes, namely, LTB4, which carries hydroxyl moieties, and the cysteinyl
LTs (LTC4, LTD4, and LTE4), which carry a cysteine amino acid moiety. Leukotriene
B4 causes adhesion and chemotactic properties. It aids in superoxide generation in
neutrophils. The cysteinyl leukotrienes are potent bronchoconstrictors and promote
vascular permeability and mucus secretion. Thus, they are regarded as the principal
components playing pathophysiological role in immediate hypersensitivity reactions. Among these, LTB4 is considered as the most potential inflammatory mediator. Agents inhibiting the biosynthesis of leukotrienes, such as LOX inhibitors, act
as potential anti-inflammatory agents.
Chemically, leukotrienes are lipid molecules with hydroxyl or amino acid moieties. The presence of three conjugated double bonds is the common feature of
leukotrienes. Based on the affinity toward different types of leukotrienes, the receptors are categorized into LTB4 receptor and cysteinyl LT receptors (cysLT1 and
cysLT2). LTB4 receptors facilitate the binding of LTB4 and thereby facilitate leukocyte infiltration and promote release of cytokines and lysosomal enzymes from
immune cells. Two receptors for the cysLTs, termed type 1 and type 2 cysLT receptors, have been identified so far (Chagnon et al. 1985; Parker 1982). These receptors
are also extensively exploited as potential anti-inflammatory targets. LTD4 is the
preferred binding agonist of the cysLT1 receptor, and LTC4 is the preferred binding
partner of the cysLT2 receptor. This triggers bronchoconstriction, migration of
eosinophils into the airways, and mucus secretion. CysLTs and their receptors are
thus considered as the chief participants in asthmatic and allergic reactions.
10.2.5 Cytokines and Sub-families
These low-molecular-weight regulatory glycoproteins propagate many vital cellular
events like immune response modulation, hematopoiesis, and inflammation. They
are primarily secreted by various cells such as macrophages and T lymphocytes in
response to a variety of immunologic or nonimmunologic stimuli. Cytokines are
categorized on the basis of their biological response and effect on immunocytes and
comprise both pro- and anti-inflammatory cytokines. Major proinflammatory cytokines include lymphokines, interferon, monokines, interleukin, colony-stimulating
factor, and tumor necrosis factor (TNF) α and β. Cytokines regulate inflammatory
B.C. Bhavya and M. Haridas