Epstein-Barr virus, cytokines, and inflammation: a cocktail for the pathogenesis of Hodgkin's lymphoma?

The association between chronic inflammation and cancer has been known for well over a century. However, direct evidence detailing the role of inflammation in carcinogenesis has been slow in forthcoming. A number of recent studies suggest that the gaps in our understanding of the molecular pathways bridging the link between inflammation and cancer are slowly beginning to close and that this relationship is more deep-rooted than had been previously believed. This review addresses the link between inflammation and Hodgkin's lymphoma (HL), a malignancy which has many features reminiscent of chronic inflammation. The role of Epstein-Barr virus (EBV) in the pathogenesis of HL is discussed, along with an outline of our current understanding of the cellular nature and development of Reed-Sternberg cells, the malignant cells of HL. The involvement of cytokines and chemokines as orchestrators of inflammation and vehicles for chemical cross-talk between the malignant cells and the reactive inflammatory infiltrate forms a major part of the review. It is suggested that chronic inflammation, triggered by factors such as EBV, is likely to contribute to tumor cell proliferation, progression, and inhibition of apoptosis. Furthermore, it is proposed that the pro-inflammatory transcription factor NF-kappaB plays a central role in many of these processes.