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The expression of the monocyte membrane glycoprotein CD14 was measured and related to the serum interferon γ (IFNγ) concentration in thirteen patients with disseminated cancer during treatment with human recombinant interferon γ (rIFNγ). The drug was administered by continuous subcutaneous infusion using an escalating dose schedule, starting at 50 µg/day or 100 µg/day and increasing weekly up to 600 µg/day, if tolerated. Treatment was continued at a mean maximal tolerated dose of 200 µg/day for a median duration of 43 days. Serum IFNγ concentration and monocyte CD14 antigen expression (immunofluorescence with the monoclonal antibody LeuM3 and fluorescence-activated cell sorting analysis) were determined weekly. The serum IFNγ concentration was positively correlated with the rIFNγ dose (P<0.05). Therapy induced a dose-dependant enhancement of CD14 antigen expression. The increase in mean CD14 fluorescence intensity was on average 60% after 3 weeks of treatment at a mean dose of 220 µg rIFNγ/day and was reversed after withdrawal of therapy. Patients with a rapidly rising serum IFNγ concentration (starting dose 100 µg/day) showed a smaller increment in CD14 fluorescence intensity than those with slowly rising serum IFNγ levels (starting dose 50 µg/day). Since rIFNγ is known to down-regulate CD14 antigen expression in vitro, monocytes from patients off therapy and from healthy volunteers were cultured with this cytokine. A similar decrease of CD14 fluorescence was observed in both groups. In patients several factors, such as IFNγ concentration, duration of drug effect and type of serum, were evaluated and could not explain the discrepant in vivo and in vitro findings. In conclusion, the monocyte marker CD14 was found to be differentially regulated by rIFNγ in vivo and in vitro. In vivo, secondary mediators, induced by rIFNγ and acting on a constantly renewed cell population, may contribute to the enhanced CD14 expression.

Summary The findings presented in this study are based on 29.226 autopsies performed (between 1953 and 1977) at Basel University on adult inhabitants of Basel, from which 409 urinary tract tumors (UTT) and 513 phenacetin abusers (PA) were discovered. There were 44 (8.6%) PA with UTT which, when compared with the control group (1.27%), represents a statistically significant increased incidence. Of the 50 UTT in PA, 52% occurred in the bladder, 6% in the ureter, and 42% in the renal pelvis. The induction time for tumors of the urinary bladder was about 27 years, and for tumors of the renal pelvis about 20 years. The commonest tumors arising in PA were invasive solid and non-invasive papillary urothelial carcinomas. PA with UTT died earlier than nonabusers but had metastases as frequently as nonabusers. Analgesic nephropathy was not always an accompanying disease. The daily dose of g/phenacetin in tumor patients in general, and in patients with tumors of the urinary bladder in particular, was about 1 g lower than in patients with analgesic nephropathy (without tumors) and in those with tumors of the renal pelvis. Thus, for the localization of the tumors, the daily dose seems to be more important than the total dose. Our investigation proved that not only tumors of the renal pelvis, but also of the ureter and the urinary bladder, are significantly more frequent in PA than in nonabusers. It is suspected that despite restriction of the over-the-counter sale of phenacetin-containing analgesics and even after stopping any analgesic abuse, UTT will further increase due to the longer induction time. Routine cytological screening tests of the urine are recommended for all known PA. A prescription for all phenacetin- and paracetamol-containing analgesics is necessary.