Prolonged interferon-gamma application by subcutaneous infusion in cancer patients: differential response of serum CD14, neopterin, and monocyte HLA class I and II antigens.
This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN-gamma) 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-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400 micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose. Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14, neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0.95, p less than 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-gamma levels (p less than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma concentrations. Second, serum neopterin and beta 2-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Landmann
R
R
Department of Research and Internal Medicine, University Hospital, Basel, Switzerland.
Ludwig
C
C
Wesp
M
M
Fisscher
A
A
Obrist
R
R
Knüsli
C
C
Denz
H
H
Obrecht
J P
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000097:blood; D004334:Drug Administration Schedule; D006680:HLA Antigens / Q000097:blood*; D006801:Humans; D007260:Infusion Pumps; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D018950:Lipopolysaccharide Receptors; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D019798:Neopterin; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin / Q000032:analysis
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D006680:HLA Antigens; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma