Increased production of tumor necrosis factor and prostaglandin E2 by monocytes in cancer patients and its unique modulation by their plasma

Abstract

We investigated the role of monocytes in the production of tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) in 77 cancer patients with malignancies of the digestive tract, using 30 normal individuals and 18 noncancer patients as controls. Monocytes were incubated with lipopolysaccharide for 20 h, and TNF production and PGE2 production were analyzed by bioassays. Elevated levels of TNF (greater than 512 U/ml) and PGE2 (greater than 8 ng/ml) production were demonstrated in many cancer patients when these factors were induced in the medium with 10% fetal bovine serum. The elevated level of TNF was seen to be restricted for the most part to patients with malignancies. Thus, 51 out of 59 cancer patients (86%), consisting of 44 primary cancer patients and 15 recurrent cancer patients, showed an increased level of TNF. In contrast, almost all of 18 postoperative cancer patients showed TNF levels comparable to those of normal individuals. Furthermore, 16 primary cancer patients were also demonstrated to have reduced levels of TNF production by monocytes after curative operation. When 10% cancer-patient plasma was added to the induction culture, TNF production by monocytes was drastically suppressed in the cancer patients. Interestingly, the same addition of plasma induced a prominent enhancement of PGE2 production in the cancer patients. The plasma of noncancer patients did not modulate production of these factors. No TNF activity was found in the plasma of cancer patients, but such plasma did contain an increased level of PGE2 (100-300 pg/ml). Although PGE2 (greater than 2 ng/ml) was able to suppress TNF production by monocytes, the addition of 10% plasma PGE2 was not enough to induce suppression. An unknown factor(s) in the plasma of cancer patients may uniquely modulate the elevated TNF and PGE2 production in these patients.

Preoperative interleukin‐6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma

“…31,32 In the present study lipopolysaccharide (LPS)-induced IL-6 production by peripheral blood mononuclear cells (PBMCs) from colorectal cancer patients was determined preoperatively and a possible correlation to the prognosis of these patients was analyzed.…”

Cytokines produced by blood mononuclear cells stimulated with the streptococcal preparation OK-432: effect on production by supplementing the medium with xenogeneic serum

“…The TNF activity of test samples was analyzed by cytotoxicity against TNF-sensitive mouse fibroblasts, L-M cells, in the presence of 1 ~g/ml actinomycin D [11]. Briefly, twofold diluted culture supernatants (0.1 ml) were added to the L-M cell monolayer culture of a plastic microplate with 96 flat-bottomed wells, and the mixtures incubated for 20 h in the presence of actinomycin D. After incubation, the cultured cells were stained with crystal violet, and absorbance determined using a micro ELISA autoreader.…”

Tumor Cell-Induced TNF Production

“…This could account for the enhanced serum levels of TNF found in tumor patients [6,7] and for the cytostatic activity of monocytes from Cancer patients [8,9]. It is not excluded that other cells besides monocytes could also be stimulated for TNF production.…”

“…Even though there is conflicting evidence concerning the presence of TNF in serum from Cancer patients [6,7,15], production in tumor tissue has been reported by several groups [5,6,10,11]. In one report, TNF was probably produced by the tumor cells [11] while in the others the host cells were the more likely producers.…”

“…Several reports describe the correlation of monocyte/macrophage activation and TNF production in a host with tumor bürden [6][7][8][9]. We therefore investigated in vitro whether tumor cells could stimulate human peripheral blood monocytes from healthy donors to synthesize TNF and IL-1 [4].…”