The pathogenesis of Crohn's disease

Although much progress has been made in understanding the pathogenesis of Crohn's disease, the precise etiology of Crohn's disease still remains unknown. In our serial studies on Crohn's disease, we found a decrease in NK and ADCC activities as well as a decrease in the phagocytic activity by monocytes, whereas an increased superoxide production activity by monocytes was evident. On the other hand, the characterization of lymphocyte subsets has demonstrated no abnormalities. According to these findings, I would like to propose a new tentative hypothesis for the pathogenesis of Crohn's disease. It has been suggested that impaired killing system activities, such as phagocytic as well as NK and ADCC activities, are primarily responsible for the promotion and perpetuation of chronic inflammation and ulceration. When our attention is directed to the common target substances of these protective mechanisms, viral antigens appear as the most likely causative organism. Therefore, a lot of attention must be focused on viral infection as a causative factor. Furthermore, effects of psychological and physical stress on the disease onset or the recurrence of inflammatory bowel disease are also discussed.