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.

Abstract

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.

• Authors: Naoyoshi Terakawa, Sohei Satoi, Soichiro Takai, Hiroaki Yanagimoto, Kanji Takahashi, Yutaka Komiyama, Kwon A-Hon, Yasuo Kamiyama, Hakuo Takahashi
• Journal: Pancreas (Pancreas) Vol. 33 Issue 1 Pg. 31-7 (Jul 2006) ISSN: 1536-4828 [Electronic] United States
• PMID: 16804410 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• Deoxycytidine
• Fluorouracil
• Gemcitabine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Hepatocellular (blood, immunology)
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Female
• Fluorouracil (therapeutic use)
• Humans
• Immunity, Cellular
• Lipopolysaccharides
• Liver Neoplasms (blood, immunology)
• Macrophages (immunology, metabolism)
• Male
• Middle Aged
• Monocytes (immunology, metabolism)
• Pancreatectomy
• Pancreatic Neoplasms (blood, drug therapy, immunology, surgery)
• Survival Analysis
• Tumor Necrosis Factor-alpha (biosynthesis)
• Gemcitabine