Clinical monitoring of innate cellular immunity of monocytes/macrophages by tumor necrosis factor alpha productivity in whole blood stimulated by lipopolysaccharide in patients with pancreatic cancer.
OBJECTIVE
The aim of this study was to evaluate the tumor necrosis factor alpha (TNF-alpha) releasing capacity in whole blood stimulated by lipopolysaccharide (LPS) in patients with pancreatic cancer during the perioperative period, and before and after chemotherapy.


METHODS
The current study involved a total of 39 patients with pancreatic cancer (PC), who were further divided into a PC-Op group (n = 16, underwent pancreatectomy) and a PC-chemo group (n = 23, received chemotherapy). The control groups consisted of patients with hepatocellular carcinoma (n = 27, HCC group) and with benign diseases (n = 15, control group). Serial changes in TNF-alpha in whole blood stimulated by LPS were compared in various clinical settings.


RESULTS
Preoperative TNF-alpha levels in the PC-Op group were significantly lower than those in the HCC and control groups (P = 0.034). The TNF-alpha variable surgical index (s-index) was defined as the ratio of the preoperative TNF-alpha level to postoperative level in the PC-Op and HCC groups. Although the TNF-alpha s-index in the PC-Op group was significantly decreased on postoperative day 1 and recovered on postoperative day 3 (P < 0.002), there were no significant changes in the TNF-alpha s-index in the HCC group. The TNF-alpha variable chemotherapeutic index (c-index) was defined as the ratio of the TNF-alpha level before to that after chemotherapy in the PC-chemo group. The TNF-alpha c-index in all 7 patients was reduced to less than 0.3 until leukopenia appeared. Patients who had an increase in TNF-alpha production (TNF-alpha c-index >1.0) on day 3 or 7 after chemotherapy had significantly better cumulative survival than those with no increase (P < 0.033).


CONCLUSIONS
TNF-alpha production stimulated by LPS in the whole blood of patients with pancreatic cancer was low. Surgical stress and depressed immunocompetence might induce such profound decreases. A method of assessing the capability of leukocytes, particularly macrophages, to produce TNF-alpha could be useful for prognostis and for monitoring immunocompetence in patients with pancreatic cancer who have undergone chemotherapy.
Terakawa
Naoyoshi
N
Departments of Surgery, Kansai Medical University, Osaka, Japan.
Satoi
Sohei
S
Takai
Soichiro
S
Yanagimoto
Hiroaki
H
Takahashi
Kanji
K
Komiyama
Yutaka
Y
A-Hon
Kwon
K
Kamiyama
Yasuo
Y
Takahashi
Hakuo
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007111:Immunity, Cellular; D008070:Lipopolysaccharides; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine