245
bridge between innate and adaptive immunities. The activation of macrophages and
lymphocytes in adaptive immune response would further augment the release of
inflammatory mediators resulting in prolonged inflammation. The prolonged activation and accumulation of macrophages stimulate undesired immune reactions
resulting in host cell damage accompanied by fibrosis. The damage and perturbation of homeostasis of the host system is regarded as a prime hallmark of chronic
inflammation. The major cellular components in chronic inflammatory response are
macrophages, lymphocytes, plasma cells, and fibroblasts. The chief chemical mediators involved in the development of chronic inflammatory responses include IFNγ, TNF-α, and interleukins. TNF-α is a prominent cytokine found to play a crucial
role in the development and progression of many immune-mediated diseases in
which the ongoing chronic inflammatory response serves as a major contributing
factor. Diseases such as rheumatoid arthritis, inflammatory bowel disorder, asthma,
psoriasis, psoriatic arthritis, and ankylosing spondylitis are some with direct link to
altered TNF activity. Controlling TNF activation by various means to reduce the
inflammatory response toward ameliorating disease symptoms has been viewed as
a potent therapeutic approach. TH1 cells, NK cells, and TC cells release IFN, while
activated macrophages secrete TNF-α. IFN-γ can activate macrophages, and these
activated macrophages overexpress class II MHC molecules. This leads to increased
cytokine production and bactericidal activity with the release of more hydrolytic
enzymes, ROS, and nitrogen intermediates which could eventually cause in-depth
damage to tissues, thus aggravating the process of inflammation. TNF-α contributes
to much of the tissue wasting associated with chronic inflammation. Activation of
macrophages by TNF-α promotes its own transactivation and production. Moreover,
TNF-α can act synergistically with IFN-γ to initiate chronic inflammation while
inducing increased expression of ICAM-1 (intercellular adhesion molecule 1),
E-selectin, and class I MHC molecules. This further facilitates the hyperinflux of
cells to the site of inflammation and promotes tissue damage. This perpetual accumulation of immune cells at the site leads to fibrosis and granuloma formation,
which are the major hallmarks of chronic inflammation. The persistent activation of
macrophages leads to the formation of high endothelial venules (HEV) along the
vasculature in the tertiary extralymphoid site of chronic infection or damage. This
HEV-like region acts as the hub to recruit more leukocytes into the site, thus aggravating inflammatory response with the destruction of the normal cell as well. The
extended inflammatory response consequently worsens the physiological and
immunological balance of the host and consequences are manifested as pathogenic
conditions. This HEV-like region has been observed in many chronic inflammatory
diseases, including RA, Crohn’s disease, ulcerative colitis, Graves’ disease, ankylosing spondylitis, Hashimoto’s thyroiditis, diabetes mellitus (Kadioglu and Sheldon
1996). Many disease conditions like hypertension, fibromyalgia, depression, etc.,
are reported to have inflammatory connections. Chronic inflammation is also associated with many autoimmune, hypersensitive, and neuroinflammatory diseases.
The inadequately regulated chronic inflammation is a major risk factor for the
development of many types of cancer.
10 Anti-inflammatory Molecules: Immune System Mediators
bridge between innate and adaptive immunities. The activation of macrophages and
lymphocytes in adaptive immune response would further augment the release of
inflammatory mediators resulting in prolonged inflammation. The prolonged activation and accumulation of macrophages stimulate undesired immune reactions
resulting in host cell damage accompanied by fibrosis. The damage and perturbation of homeostasis of the host system is regarded as a prime hallmark of chronic
inflammation. The major cellular components in chronic inflammatory response are
macrophages, lymphocytes, plasma cells, and fibroblasts. The chief chemical mediators involved in the development of chronic inflammatory responses include IFNγ, TNF-α, and interleukins. TNF-α is a prominent cytokine found to play a crucial
role in the development and progression of many immune-mediated diseases in
which the ongoing chronic inflammatory response serves as a major contributing
factor. Diseases such as rheumatoid arthritis, inflammatory bowel disorder, asthma,
psoriasis, psoriatic arthritis, and ankylosing spondylitis are some with direct link to
altered TNF activity. Controlling TNF activation by various means to reduce the
inflammatory response toward ameliorating disease symptoms has been viewed as
a potent therapeutic approach. TH1 cells, NK cells, and TC cells release IFN, while
activated macrophages secrete TNF-α. IFN-γ can activate macrophages, and these
activated macrophages overexpress class II MHC molecules. This leads to increased
cytokine production and bactericidal activity with the release of more hydrolytic
enzymes, ROS, and nitrogen intermediates which could eventually cause in-depth
damage to tissues, thus aggravating the process of inflammation. TNF-α contributes
to much of the tissue wasting associated with chronic inflammation. Activation of
macrophages by TNF-α promotes its own transactivation and production. Moreover,
TNF-α can act synergistically with IFN-γ to initiate chronic inflammation while
inducing increased expression of ICAM-1 (intercellular adhesion molecule 1),
E-selectin, and class I MHC molecules. This further facilitates the hyperinflux of
cells to the site of inflammation and promotes tissue damage. This perpetual accumulation of immune cells at the site leads to fibrosis and granuloma formation,
which are the major hallmarks of chronic inflammation. The persistent activation of
macrophages leads to the formation of high endothelial venules (HEV) along the
vasculature in the tertiary extralymphoid site of chronic infection or damage. This
HEV-like region acts as the hub to recruit more leukocytes into the site, thus aggravating inflammatory response with the destruction of the normal cell as well. The
extended inflammatory response consequently worsens the physiological and
immunological balance of the host and consequences are manifested as pathogenic
conditions. This HEV-like region has been observed in many chronic inflammatory
diseases, including RA, Crohn’s disease, ulcerative colitis, Graves’ disease, ankylosing spondylitis, Hashimoto’s thyroiditis, diabetes mellitus (Kadioglu and Sheldon
1996). Many disease conditions like hypertension, fibromyalgia, depression, etc.,
are reported to have inflammatory connections. Chronic inflammation is also associated with many autoimmune, hypersensitive, and neuroinflammatory diseases.
The inadequately regulated chronic inflammation is a major risk factor for the
development of many types of cancer.
10 Anti-inflammatory Molecules: Immune System Mediators