Intraperitoneal fluid neopterin, nitrate, and tryptophan after regional administration of interleukin-12.
Activated monocytes-macrophages may be associated with antitumor activity, and activation of these cells by certain cytokines, primarily interferon gamma (IFN-gamma), can be indicated by alterations in the concentrations of neopterin, nitrate, or tryptophan. Specimens of peritoneal fluid were obtained from patients with intra-abdominal neoplasia who were undergoing treatment in a phase I trial of weekly intraperitoneal recombinant interleukin-12 (rhIL-12), an inducer of IFN-gamma. Concentrations of neopterin, nitrate, tryptophan, IFN-gamma, and tumor necrosis factor alpha (TNF-alpha) were determined at various times during the first 48 hours in 11 patients who received intraperitoneal rhIL-12 in doses ranging from 100 to 1,500 ng/kg. An increase in peritoneal fluid nitrate concentrations was observed in nine of these patients. Increased concentrations of TNF-alpha and IFN-gamma were detected in 3 of 9 and 8 of 11 patients, respectively. Increased peritoneal fluid neopterin concentrations were detected by 24 hours after the injection in all patients studied. A significant increase in the ascitic fluid neopterin level could still be detected after 1 or 2 weeks of treatment (mean +/- standard error, 7.8 +/- 1.5 nM vs. 4.6 +/- 0.3 nM; Wilcoxon test, p = 0.0019), which is consistent with monocyte-macrophage activation. In contrast, the tryptophan concentration was lower (4.7 +/- 1.1 microM vs. 6.1 +/- 1.2 microM; p = 0.0428) after 1 or 2 weeks of treatment. There was a significant correlation between the dose of rhIL-12 and posttreatment neopterin concentrations (r(s) = 0.559, p = 0.0102). The intraperitoneal delivery of rhIL-12 appears to be associated with an immediate, sustained, and dose-dependent increase in peritoneal fluid neopterin, associated in most patients by an increase in IFN-gamma and in certain patients by an increase in nitrate and a decrease in tryptophan concentrations.
Melichar
Bohuslav
B
Department of Gynecologic Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Lenzi
Renato
R
Rosenblum
Michael
M
Kudelka
Andrzej P
AP
Kavanagh
John J
JJ
Melicharova
Karolina
K
Templin
Stacie
S
Garcia
Michael E
ME
Abbruzzese
James L
JL
Freedman
Ralph S
RS
D000008:Abdominal Neoplasms / Q000188:drug therapy; D001202:Ascitic Fluid / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage*; D019798:Neopterin / Q000032:analysis*; D009566:Nitrates / Q000032:analysis*; D011994:Recombinant Proteins / Q000008:administration & dosage; D014364:Tryptophan / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D009566:Nitrates; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan