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.