Original ArticlesDevelopmental Phases of Inflammation-Induced Massive Lymphoid Hyperplasia and Extensive Changes in Epithelium in an Experimental Model of Allergy Implications for a Direct Link Between Inflammation and CarcinogenesisKhatami, Mahin* Author Information University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. The studies were supported by NIH grants EY-03984 and EY-06616; Fight for Sight, Inc., New York; unrestricted grants from Research to Prevent Blindness, New York; the Gretel and Eugene Ormandy Teaching and Research Fund, Philadelphia; the Juvenile Diabetes International Foundation Summer Student Programs, New York; and the Food and Agricultural Organization/UN Development Program/World Bank/WHO. *Address for correspondence: The National Cancer Institute, Division of Cancer Prevention, National Institutes of Health, 3151 EPN, 1630 Executive Plaza, Bethesda, MD 20892. E-mail: [email protected] American Journal of Therapeutics: March 2005 - Volume 12 - Issue 2 - p 117-126 doi: 10.1097/01.mjt.0000143699.91156.21 Buy Metrics Abstract Direct evidence that inflammation is linked to carcinogenesis has yet to be established. Very few data are available on the developmental phases of inflammation-induced immune dysfunction that may lead to tumorigenesis. In a series of studies conducted in the 1980s and 1990s, an experimental model of acute and chronic inflammation was established in guinea pig conjunctiva by topical application of fluoresceinyl ovalbumin (FLOA) for up to 30 months. In this updated report, some of the findings are reanalyzed and expanded to identify that at lease 3 developmental phases were involved during the entire course of inflammatory responses including (1) an acute response (phase A) involving IgE-mast cell sensitization and degranulation; (2) an intermediate phase (phase B), a desensitization phenomenon and loss of mast cell function and neovascularization; (3) a chronic response (phase C) and induction of massive lymphoid hyperplasia, follicular formation with germinal centers, increased swollen goblet cells, extensive epithelial thickening and thinning, and angiogenesis. The results suggest evidence of a direct association between inflammation and the development of tumor-like lesions in lymphoid tissues and extensive changes in adjacent epithelia. Confirmation that inflammation induces irreversible changes in lymphoid and epithelial tissues leading to lymphoid tumorigenesis and/or carcinogenesis requires further studies. Understanding the developmental phases of immune dysfunction may provide unique opportunities for diagnosis and treatment of inflammatory diseases, autoimmune disorders, and cancers including lymphomas associated with Sjögren syndrome, squamous cell carcinoma of the conjunctiva, and other lymphomas or epithelial cancers. It is suggested that inflammatory mediators are ideal targets (biomarkers) for diagnosis, chemoprevention, and therapy for several cancers. © 2005 Lippincott Williams & Wilkins, Inc.