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. 1990 Sep 1;31(5):292–296. doi: 10.1007/BF01740937

Recombinant interferon γ up-regulates in vivo and down-regulates in vitro monocyte CD14 antigen expression in cancer patients

R Landmann 1,✉, M Wesp 2, C Ludwig 1, R Obrist 1, C Knüsli 1, J P Obrecht 1
PMCID: PMC11038503  PMID: 1695870

Abstract

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.

Keywords: Mononuclear Leukocyte, Recombinant Interferon, Continuous Subcutaneous Infusion, CD14 Antigen Expression, Monocyte CD14

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