SOLUBLE URINARY CD14 AFTER INTRAVESICAL BACILLE CALMETTE-GUERIN IMMUNOTHERAPY FOR CARCINOMA IN-SITU

Objective To characterize the production of the monocyte activation ma rker, soluble CD14 (sCD14), after bacille Calmette-Guerin (BCG) immuno therapy for superficial bladder cancer. Patients and methods Nineteen patients with carcinoma in situ were treated with a standard regimen o f intravesical BCG. Urine samples were collected after each instillati on and analysed; the levels of soluble CD14 were determined by an enzy me-linked immunosorbent assay, the molecular weight confirmed by Weste rn blotting and the possible cell source investigated using immunohist ochemistry. Results The mean levels of sCD14 were higher in patients w ith persistent carcinoma (designated as failures) than in those who ha d successful complete responses (responders) to BCG immunotherapy. The differences were statistically significant, with P=0.034 at instillat ion 4 and P=0.027 at instillation 5 for the total mass of sCD14, and P =0.049 at instillation 4 for the concentration of sCD14. The predomina nt type of sCD14 in urine was the 48 kDa form, although in most patien ts there was a minor band of reactivity at 54 kDa. A panel of human bl adder cancer cell lines did not react with the anti-CD14 monoclonal an tibodies 3C10, 5C5 and BA8, and the antibodies also failed to react wi th malignant epithelial cells in frozen sections of untreated bladder tumour. Furthermore, sCD14 was not secreted by cultured bladder tumour cells. The source of urinary sCD14 is likely to be the resident and i nfiltrating macrophages in the bladder wall. Freshly isolated peripher al blood monocytes secreted sCD14 in response to BCG in a manner analo gous to stimulation with bacterial lipopolysaccharide.Conclusion A sol uble form of CD14 is secreted into the urine of patients who receive i ntravesical BCG. The measurement of soluble urinary CD14 could be of p rognostic significance for the response to immunotherapy.