Urinary cytokines reflecting the immunological response in the urinary bladder to biological response modifiers: their practical use

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) immunotherapy is currently the most effective treatment for superficial transitional cell carcinoma (TCC) of the urinary bladder. In recent years, the substantial number of patients not responding to BCG or experiencing considerable toxicities has stimulated studies addressing either the development of improved BCG treatment schedules or the exploration of the therapeutic value of a series of (novel) biological response modifiers, like interferons (IFNs), interleukin (IL) 2 and keyhole limpet hemocyanin. Although the actual mechanism by which BCG exerts its antitumor effect still needs detailed unraveling, current available knowledge suggests the induction of a T helper 1 (Th1) or Th1-like cytokine profile, represented by IL-2, IL-12 and IFN-gamma, as essential in the development of a cell-mediated antitumor activity. CONCLUSIONS: In this review, it is argued that incorporation of urinary cytokine determinations, like IL-2 and possibly IL-12 and IFN-gamma, may represent a valuable approach in the optimization and individualization of the BCG therapy and an early, initial evaluation of the potential efficacy of novel immunomodulating agents in the treatment of superficial TCC