Inflammatory Mediators May Have Divergent Roles in Cancer and in Alzheimer's Disease

Abstract

To the Editor: The April 2010 issue of Clinical Pharmacology & Therapeutics focuses on the role of inflammation in the pathogenesis of cancer, obesity, and cardiovascular disease. However, another important disease with an inflammatory component, Alzheimer’s disease (AD), receives only limited attention.1 Epidemiologic studies indicate an inverse association between the incidence of AD and that of cancer;2 on the other hand, there is a direct association between the incidence of both diabetes and cardiovascular disease and that of AD.3 The contribution of immune processes to the pathogenesis of these diseases is now becoming more fully appreciated. For instance, the progression of AD has been correlated with immune processes that promote or inhibit disease progression involving the innate immune system through alterations in the clearance of amyloid by the complement protein C1q, elevation of levels of inflammatory cytokines that worsen amyloid deposition, activation of amyloid protein processing,4 and alteration of the receptor for advanced glycolytic end products. Our current understanding of the importance of the innate and adaptive immune system in cancer immunosurveillance can help us to conceptualize a similar paradigm for other diseases, such as AD. The cancer immunosurveillance hypothesis proposes that the differences between no disease, a smoldering disease state, and progression are dependent on the shift in balance between a tolerogenic protumor immune state and an active antitumor response. Similarly, the pathogenesis of AD is likely to be influenced by a variety of intrinsic and extrinsic factors, including the age of the immune system, neurovascular health, tissue damage, and infection. The same proinflammatory responses that contribute to an antitumorigenic response in neoplastic disease may promote tissue destruction and exacerbation of AD. Conversely, the tolerogenic protumor immune responses may be beneficial to AD patients. This model may explain the observed inverse association between the two diseases. The decreased or delayed occurrence of cancer in AD patients might be due to the nature of the immune response in these individuals, favoring AD progression while retarding cancer development. In effect, the production of mediators as by-products of the inflammatory process activated during the amyloid cascade in AD patients may be “good” for inhibiting cancer development but “bad” because they may promote AD.5 An improved understanding of the dynamics of the immune environment in AD and cancer is likely to lead to novel therapeutic approaches that shift the immune balance to a more favorable clinical outcome.