Prolonged Interferon-γ Application by Subcutaneous Infusion in Cancer Patients: Differential Response of Serum CD14, Neopterin, and Monocyte HLA Class I and II Antigens

Publisher Website
Google Scholar
Abstract
This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-γ (rIFN-γ) with particular attention to changes of soluble CD14. This glycoprotein with an unknown function is derived from myeloid cells carrying membrane CD14, which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP) complexes. Fifteen metastatic cancer patients received weekly escalating doses of rIFN-γ starting at either 50 or 100 μg/24 h and increasing up to 400 μg/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 μg/24 h) with the lower (50 μg/24 h) starting dose. Biological activity of rIFN-γ was evaluated by weekly measurements of CD14, neopterin, and β2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-γ concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0,95, p < 0,05). Among the biological markers, two patterns were observed. First, serum CD14 concentration and expression of monocyte HLA class II antigens increased significantly during the first week, and marker expression correlated with serum IFN-γ levels (p < 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-γ concentrations. Second, serum neopterin and β2-microglobulin concentrations as well as monocyte HLA class I expression also increased significantly within the first week, but remained elevated thereafter without any further dose relationship. In conclusion, during a well-tolerated continuous s.c. infusion of rIFN-γ, marked biological activity of monocytes is achieved. The IFN-γ–induced elevation of CD14 may indicate an immunomodulatory role for this molecule.