Journal
EXPERT OPINION ON BIOLOGICAL THERAPY
Volume 11, Issue 11, Pages 1419-1432Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14712598.2011.592826
Keywords
acute and chronic inflammation; angiogenesis; autoimmune; cancer; BBB; CNS; cornea; dendritic cells; hyperplasia; immune-privilege; immune surveillance; immune tolerance; innate and adaptive immune cells; macrophages; mast cells; natural killer cells; neovascularization; neurodegenerative; neuroretina; tissue integrity
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Introduction: Unresolved inflammation is loss of balance between two biologically opposing arms of acute inflammation, 'Yin' (tumoricidal) and 'Yang' (tumorigenic) processes that cause disruption of protective mechanisms of immune system. Areas covered: Hypothesis: Unresolved inflammation-induced exaggerated expression of apoptotic and/or wound healing mediators lead to fundamental erosion ('immune tsunami' or 'immune meltdown') of integrity in tissues that are naturally immune-responsive (immune surveillance); or immune-privileged (immune tolerance). 'Immune tsunami' refers to end results of acute or chronic immune dysfunction leading to inflammatory diseases or cancer. Acute inflammatory diseases including drug-induced cancer cachexia, would fit features of 'immune meltdown' that are otherwise described for end results of age-associated diseases. Pathogens induce rapid destruction of vascular integrity, gain access to tissues and cause excessive expression of apoptotic factors leading to multiple organ failure (MOF). Significant disruptions of immunological barriers and response shifts lead to chronic neurodegenerative and autoimmune diseases, tumor growth, malignancies and angiogenesis and loss of natural immune response balances. Expert opinion: Strategies to promote (stabilize) inherent properties of innate immune cells ('tumoricidal' versus 'tumorigenesis') that would influence polarization of adaptive immune (T or B) cells are key in reducing or preventing incidence of inflammatory and vascular diseases or cancer during aging process.
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