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which get accumulated at the joints. These immune complexes can further activate
the complement split products, resulting in a type III hypersensitive reaction, which
ultimately causes chronic inflammation of the joint. RA pathogenesis is multifactorial and no specific treatment is resolved yet. However, NSAIDs are used more
frequently. TNF-α blockers and complement inhibitors are other promising therapeutic options. Infliximab (Remicade) is a human monoclonal chimeric antibody
against TNF-α approved clinically for treating RA as well as for Crohn’s disease.
Multiple sclerosis is a neurologic disability afflicting multiple parts of the body
characterized by an ongoing autoimmune response against the central nervous system. Hyperactivated autoreactive T cells form inflammatory lesions, with severe
damage on the myelin sheath of nerve fibers; however, the inflammatory aspect is
not well established. IFNs (IFN 1α and β) are the major cytokines with a beneficial
role in suppressing autoimmune response in MS (Owens 2003). Aberrant TNF activation has also been linked with the development of MS. Steroids are recommended
for acute episodes as anti-inflammatory therapy for Multiple Sclerosis (MS).
However, Avonex and Rebif with IFN 1α- and β-protein-expressing drugs are found
effective in treating progressive MS conditions.
10.4 Inflammatory Mediators in Disease Pathogenesis
10.4.1 Complement in Pathogenesis
Inappropriate complement activation participates in the pathogenesis of many
immune disorders such as inflammatory and autoimmune diseases. Apart from
these, complement hyperactivation is reported in neurodegenerative, infectious, and
metabolic disorders. Elevated levels of complement by-products are found in plasma
samples of RA and systemic lupus erythematosus patients. Complement fragments
at higher levels are reported in the serological samples of patients suffering from
Crohn’s disease, psoriasis, asthma, age-related macular degenerating lupus erythematosus, multiple sclerosis, myocardial infarction, atypical hemolytic uremic syndrome, and stroke. Complements are also involved in ischemia, reperfusion-mediated
kidney injury, transplant rejections, and carcinogenesis. Complement inhibition is
thus recognized as a possible solution to ameliorate the severity of these diseases.
Complements play a vital function in organ transplantation, especially in graft
rejection associated with kidney transplantation, by triggering adverse effects on the
graft.
10.4.2 Histamine in Pathogenesis
The role of histamine in disease pathogenesis is determined by the receptor subtype
it gets to interact with. Histamine is primarily involved in allergic manifestations.
H1R receptor is involved in smooth-muscle constriction and mucus production,
resulting in dysmenorrhea and respiratory discomfort. H2R affects gastric acid
10 Anti-inflammatory Molecules: Immune System Mediators
which get accumulated at the joints. These immune complexes can further activate
the complement split products, resulting in a type III hypersensitive reaction, which
ultimately causes chronic inflammation of the joint. RA pathogenesis is multifactorial and no specific treatment is resolved yet. However, NSAIDs are used more
frequently. TNF-α blockers and complement inhibitors are other promising therapeutic options. Infliximab (Remicade) is a human monoclonal chimeric antibody
against TNF-α approved clinically for treating RA as well as for Crohn’s disease.
Multiple sclerosis is a neurologic disability afflicting multiple parts of the body
characterized by an ongoing autoimmune response against the central nervous system. Hyperactivated autoreactive T cells form inflammatory lesions, with severe
damage on the myelin sheath of nerve fibers; however, the inflammatory aspect is
not well established. IFNs (IFN 1α and β) are the major cytokines with a beneficial
role in suppressing autoimmune response in MS (Owens 2003). Aberrant TNF activation has also been linked with the development of MS. Steroids are recommended
for acute episodes as anti-inflammatory therapy for Multiple Sclerosis (MS).
However, Avonex and Rebif with IFN 1α- and β-protein-expressing drugs are found
effective in treating progressive MS conditions.
10.4 Inflammatory Mediators in Disease Pathogenesis
10.4.1 Complement in Pathogenesis
Inappropriate complement activation participates in the pathogenesis of many
immune disorders such as inflammatory and autoimmune diseases. Apart from
these, complement hyperactivation is reported in neurodegenerative, infectious, and
metabolic disorders. Elevated levels of complement by-products are found in plasma
samples of RA and systemic lupus erythematosus patients. Complement fragments
at higher levels are reported in the serological samples of patients suffering from
Crohn’s disease, psoriasis, asthma, age-related macular degenerating lupus erythematosus, multiple sclerosis, myocardial infarction, atypical hemolytic uremic syndrome, and stroke. Complements are also involved in ischemia, reperfusion-mediated
kidney injury, transplant rejections, and carcinogenesis. Complement inhibition is
thus recognized as a possible solution to ameliorate the severity of these diseases.
Complements play a vital function in organ transplantation, especially in graft
rejection associated with kidney transplantation, by triggering adverse effects on the
graft.
10.4.2 Histamine in Pathogenesis
The role of histamine in disease pathogenesis is determined by the receptor subtype
it gets to interact with. Histamine is primarily involved in allergic manifestations.
H1R receptor is involved in smooth-muscle constriction and mucus production,
resulting in dysmenorrhea and respiratory discomfort. H2R affects gastric acid
10 Anti-inflammatory Molecules: Immune System Mediators