Localization of IL-1, IL-2, IL-4, IL-8 and TNF in superficial bladder tumors treated with intravesical bacillus Calmette-Guerin.
OBJECTIVE
Cytokines have been detected in the urine during the first hours after intravesical Bacillus Calmette Guerin (BCG) treatment against superficial bladder cancer. To investigate the long-lasting mucosal inflammatory response, we analyzed intracellular cytokines by immunohistochemistry in biopsies taken 2 weeks after BCG treatment.


METHODS
Tumor biopsies were obtained from 8 patients with noninvasive, papillary transitional cell carcinoma (TCC), and intracellular cytokines were visualized by immunohistochemistry using cytokine-specific monoclonal antibodies.


RESULTS
Interleukin (IL)-1 beta+ or tumor necrosis factor (TNF)-alpha+ cells were abundant in tumor and stroma. Interleukin-1 alpha, IL-2, IL-4, IL-8 and TNF-beta were variably expressed, while IL-10+ and interferon (IFN)-gamma+ cells were not detected. Among the few patients studied (5 responders and 3 nonresponders to BCG treatment) no single cytokine or cytokine profile was associated with clinical response to BCG therapy.


CONCLUSIONS
We conclude that the in situ cytokine response after BCG treatment is highly complex, since cytokine profiles differed among the 8 patients investigated and between tumor and surrounding tumor-free mucosa. Further studies, investigating larger numbers of patients, is required to clarify whether cytokine profiles correlate with the clinical response to BCG.
Sander
B
B
Department of Pathology 1., Faculty of Health Sciences, University of Linköping, Sweden.
Damm
O
O
Gustafsson
B
B
Andersson
U
U
Håkansson
L
L
D000283:Administration, Intravesical; D001500:BCG Vaccine / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000378:metabolism / Q000628:therapy; D004396:Coloring Agents; D006801:Humans; D007378:Interleukins / Q000032:analysis* / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000628:therapy
D001500:BCG Vaccine; D004396:Coloring Agents; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha