Towards an understanding of the mode of action of Bacillus Calmette-Guérin-therapy in bladder cancer treatment, especially with regard to the role of fibronectin.

The interaction between Bacillus Calmette-Guérin (BCG) and the host was investigated after repeated intravesicular BCG-therapy for superficial bladder cancer. Studies were performed on (a) the local reaction in the bladder, (b) the systemic reaction, and (c) short and long term interactions in both the bladder and the serum/plasma. The analytes measured included anti-BCG IgA and IgG, fibronectin, lactoferrin, elastase-alpha 1-proteinase inhibitor, myeloperoxidase and alpha 2-proteinase inhibitor. All analytes, with the exception of alpha 2-proteinase inhibitor, were measured in both serum/plasma and urine. An additional group of 94 patients undergoing bronchoalveolar lavage was used for comparison with other diseases affecting mucous membranes. In vitro studies on human bladder in culture were also carried out to study the relationship between BCG, elastase and fibronectin. The results revealed a normal defence reaction, in which IgA and IgG antibodies specific to BCG were produced by the host. Maximal concentrations of all analytes in urine were found about 4 h after BCG instillation. Immunoglobulins, soluble fibronectin, and granulocyte markers all appeared in urine after instillation and all showed a similar time course. The in vitro study showed the synergistic effect of elastase and BCG in stimulating the host defence reaction. The relationship between BCG and fibronectin can be seen as fortuitous but not indicative of the efficacy of BCG-therapy in patients with superficial bladder cancer.