In vivo tumor necrosis factor-alpha as indicator of biologic and clinical response to low-dose SC recombinant interleukin 2.
The effect of low-dose human recombinant interleukin-2 (rIL-2) on the induction of secondary tumor necrosis factor-alpha (TNF-alpha) in vivo was studied in 16 patients with metastatic renal cell carcinoma. In all patients s.c. rIL-2 resulted in a significant increase in TNF-alpha serum levels within 4 to 8 hours, as determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha serum concentrations remained elevated up to 24 hours following single s.c. administration of rIL-2. Total secondary TNF-alpha release, as assessed by the area under the curve (AUC), appeared to be independent of dose distribution of rIL-2 (10 million IU rIL-2 q12 hours versus 20 million IU rIL-2 q24 hours). rIL-2 induced TNF-alpha release was significantly higher in patients who had received prior rIL-2 immunotherapy, while steroids resulted in a significant suppression of TNF-alpha release. Secondary TNF-alpha release was statistically associated with progression-free survival of renal cell carcinoma patients and may be a prognostic factor in patients receiving rIL-2.
Meffert
M
M
Division of Hematology and Oncology, Medizinische Hochschule Hannover, Germany.
Schomburg
A
A
Hänninen
E L
EL
Menzel
T
T
Vocke
S
S
Dallmann
I
I
Grosse
J
J
Duensing
S
S
Buer
J
J
Kirchner
H
H
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000628:therapy*; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D015415:Biomarkers; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha