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Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized
inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the
gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic
changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as
enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor
necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced,
TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and
IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD,
using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current
therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs
like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.
ROLE OF INFECTION AND CHRONIC INFLAMMATION IN THE PATHOGENESIS OF NON-HODGKINS LYMPHOMA
