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10.3.1 Auto-inflammatory Diseases
Ongoing inflammatory response may act as the primary trigger for the development
of certain diseases. It includes inflammatory, hypersensitive, autoimmune, and neurodegenerative diseases. Inflammatory reactions play a primary role in the pathophysiological conditions such as allergy, Crohn’s disease and colitis, Hashimoto’s
thyroiditis, and Graves’ disease. However, in some cases, the chronic inflammatory
response may function as secondary trigger to enhancing the chance of initiation,
progression, or regression of certain diseases. Erroneous activation of many inflammatory mediators has been found to directly aggravate immune responses, contributing to the symptomatic manifestations of a variety of diseases. Overactivation of
interleukin 12 (IL-12) and IFN-γ is correlated with Crohn’s disease, and IL-13 production is associated with the pathogenesis of colitis ( Medzhitov 2008; Navab et al.
2008). TNF-α is the critical mediator of IBD pathogenesis. Moreover, TNF also
substantially influences intestinal epithelial cell growth and thus supports bacteriainduced granulomas through the induction of MCP-1 production by endothelial
cells. Inhibition of proinflammatory cytokines appears as a promising choice of
therapy.
Atheroma formation in atherosclerosis is facilitated following the hyperinflammatory signals from leukotrienes and proinflammatory cytokines like IL-1, IL-6,
and TNF-α. Inhibitors of leukotriene and phospholipase A 2 are suggested as the
plausible targets of therapy. Mycobacterium tuberculosis infection provokes chronic
inflammatory response, leading to granuloma formation and tissue damage.
Proinflammatory cytokines such as TNF-α and IL-1 and chemokines from PMN
and monocytes are overtly implicated in its pathogenesis. Proinflammatory
responses have been actively related with the onset of several neurodegenerative
disorders. However, the precise implications of the inflammatory response for neurodegenerative diseases have not been elucidated yet. IL-1b, TNF-α, and IL-6 are
the major mediators involved in the pathophysiology of Alzheimer’s disease. The
overexpression of chemokines and its receptor CCR1 is observed in the brain tissues of Alzheimer’s patients, suggesting their direct impact on neuronal cell damage. The inappropriate inflammatory response contributes severely to nerve cell
damage in the central nervous system in other neuroinflammatory diseases such as
Parkinson’s disease and multiple sclerosis.
Inflammatory response has been inseparably linked with the pathogenesis of literally all types of cancers. Cytokine signaling can contribute to the progression of
tumors either by stimulating proliferation, aiding in metastasis, promoting angiogenesis, or by conferring resistance to apoptosis (Grivennikov et al. 2010). Several
leukocyte subpopulations appear to establish an inflammatory microenvironment in
the epithelial-originated tumors. Cytokines (IL1, 6, 8, and 10, TNF-α, TGF-β, and
colony-stimulating factors) have been reported in many instances with direct regulatory role in different stages of carcinogenesis.
Chemokines play crucial functions in facilitating cancer metastasis. NFκB
(nuclear factor of kappa light polypeptide) and AP1 (activating protein 1) activated
by inflammatory stimuli are the widely studied proteins and their role in the
B.C. Bhavya and M. Haridas
10.3.1 Auto-inflammatory Diseases
Ongoing inflammatory response may act as the primary trigger for the development
of certain diseases. It includes inflammatory, hypersensitive, autoimmune, and neurodegenerative diseases. Inflammatory reactions play a primary role in the pathophysiological conditions such as allergy, Crohn’s disease and colitis, Hashimoto’s
thyroiditis, and Graves’ disease. However, in some cases, the chronic inflammatory
response may function as secondary trigger to enhancing the chance of initiation,
progression, or regression of certain diseases. Erroneous activation of many inflammatory mediators has been found to directly aggravate immune responses, contributing to the symptomatic manifestations of a variety of diseases. Overactivation of
interleukin 12 (IL-12) and IFN-γ is correlated with Crohn’s disease, and IL-13 production is associated with the pathogenesis of colitis ( Medzhitov 2008; Navab et al.
2008). TNF-α is the critical mediator of IBD pathogenesis. Moreover, TNF also
substantially influences intestinal epithelial cell growth and thus supports bacteriainduced granulomas through the induction of MCP-1 production by endothelial
cells. Inhibition of proinflammatory cytokines appears as a promising choice of
therapy.
Atheroma formation in atherosclerosis is facilitated following the hyperinflammatory signals from leukotrienes and proinflammatory cytokines like IL-1, IL-6,
and TNF-α. Inhibitors of leukotriene and phospholipase A 2 are suggested as the
plausible targets of therapy. Mycobacterium tuberculosis infection provokes chronic
inflammatory response, leading to granuloma formation and tissue damage.
Proinflammatory cytokines such as TNF-α and IL-1 and chemokines from PMN
and monocytes are overtly implicated in its pathogenesis. Proinflammatory
responses have been actively related with the onset of several neurodegenerative
disorders. However, the precise implications of the inflammatory response for neurodegenerative diseases have not been elucidated yet. IL-1b, TNF-α, and IL-6 are
the major mediators involved in the pathophysiology of Alzheimer’s disease. The
overexpression of chemokines and its receptor CCR1 is observed in the brain tissues of Alzheimer’s patients, suggesting their direct impact on neuronal cell damage. The inappropriate inflammatory response contributes severely to nerve cell
damage in the central nervous system in other neuroinflammatory diseases such as
Parkinson’s disease and multiple sclerosis.
Inflammatory response has been inseparably linked with the pathogenesis of literally all types of cancers. Cytokine signaling can contribute to the progression of
tumors either by stimulating proliferation, aiding in metastasis, promoting angiogenesis, or by conferring resistance to apoptosis (Grivennikov et al. 2010). Several
leukocyte subpopulations appear to establish an inflammatory microenvironment in
the epithelial-originated tumors. Cytokines (IL1, 6, 8, and 10, TNF-α, TGF-β, and
colony-stimulating factors) have been reported in many instances with direct regulatory role in different stages of carcinogenesis.
Chemokines play crucial functions in facilitating cancer metastasis. NFκB
(nuclear factor of kappa light polypeptide) and AP1 (activating protein 1) activated
by inflammatory stimuli are the widely studied proteins and their role in the
B.C. Bhavya and M. Haridas