Cytokines IL-1beta, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNFalpha in patients with epithelial ovarian cancer and their relationship to treatment with paclitaxel.
In vitro work suggests that cytokines may be important modulators of the cytotoxic effects of paclitaxel and subsequent drug resistance. This has been investigated in vivo in patients with ovarian cancer by ELISA. There was consistently elevated expression of IL-6 and IL-8 but not MCP-1, IL-1beta, IL-2, GM-CSF or TNFalpha. Peritoneal fluid concentrations of IL-6, IL-8 and MCP-1 were two to three logs greater than serum concentrations. Elevated concentrations of IL-6 correlated with a poor final outcome (P = 0.039), and increased IL-6 and IL-8 correlated with a poor initial response to chemotherapy (P = 0.041 and P = 0.041, respectively). There was a relatively clear pattern of change in all three cytokines. In serum, IL-6, IL-8 and MCP-1 decreased with the administration of steroids prior to paclitaxel, and increased in the 24 h after paclitaxel. Postoperative drainage fluid was relatively acellular, preventing flow-cytometric analysis of epithelial cells for apoptosis, but suggested activation of T cells by paclitaxel. IL-6 and IL-8 appear to be of prognostic importance in epithelial ovarian cancer. Treatment with paclitaxel is associated with an increase in expression of a limited number of cytokines in patients with ovarian cancer, notably IL-6, IL-8 and MCP-1.
Division of Hematology and Oncology; Vincent Gynecology, Division of Gynecologic Oncology;Division of Biostatistics, and Adult Oncology, Dana Farber Cancer Institute;Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
R. T.
RT
Penson
K.
K
Kronish
Z.
Z
Duan
A. J.
AJ
Feller
P.
P
Stark
S. E.
SE
Cook
L. R.
LR
Duska
A. F.
AF
Fuller
A. K.
AK
Goodman
N.
N
Nikrui
K. M.
KM
MacNeill
U. A.
UA
Matulonis
F. I.
FI
Preffer
M. V.
MV
Seiden