Mononuclear cells release low molecular weight factors with anti-cancer activity: A lower level of production by cells of cancer patients.

Following the clinical observations that tumor metastases are extremely rare in striated muscles we defined recently a low molecular weight factor which is released by muscle cells (muscle factor, MF) and possesses specific anti-proliferative activity against tumor cells. we demonstrate that peripheral blood mononuclear cells constitutively release low molecular weight factor (LMF) similar to the MF which is capable of inhibiting in vitro the proliferation of carcinoma, melanoma, leukemia and lymphoma cell lines. The proliferation of normal cells such as bone marrow or fibroblasts was not inhibited but slightly stimulated following incubation with the LMF. Biochemical purification of this factor by several HPLC steps revealed that the inhibitory activity against tumor cells was concentrated within two definitive peaks. The LMF affects tumor cell growth by arresting them in the G0/G1 of the cell cycle and its activity is species and tumor non-specific. In vivo studies in melanoma- bearing mice revealed that the LMF inhibited melanoma growth when given either intraperitoneally or orally. Mononuclear cells from cancer patients with different malignancies (non-Hodgkin lymphoma, malignant melanoma, colon carcinoma and carcinoma of the rectum) secreted lower level of LMF in comparison to healthy subjects. The capability of the LMF to inhibit tumor cell growth and promote normal cell proliferation combined with its bioavailability in vivo may lead to its potential therapeutic and diagnostic use.

Kinetics of cortisol, interleukin-2 and interleukin-3-like activity levels following surgical intervention.

Cortisol, interleukin(IL)-2 and IL-3-like activity (IL-3-LA) levels were examined in two groups of patients before and after surgery. One group consisting of 11 patients underwent cholecystectomy; the other comprising 17 patients with malignant diseases of the gastrointestinal tract underwent a removal of the tumor. In both groups there were similar fluctuations in cortisol levels after surgery, i.e. a statistically significant increase at day 2 after operation with a decrease to normal values at day 14. The levels of IL-2 and IL-3-LA production in the two groups followed a different pattern. In patients with cholecystectomy the IL-2 and IL-3-LA levels showed a marked decrease at day 2 with a gradual increase on the following days. In cancer patients IL-2 was at its lowest level before surgery and started to increase gradually till day 14 after surgery. The lowest level of IL-3-LA was at day 2 after surgery and it increased gradually from day 7 to 14. It is suggested that the fluctuations of these two cytokines after surgery are related to the levels of corticosteroids which have been shown to inhibit the production of IL-2 and IL-3-LA in vitro. The observed increase of cortisol level with a concomitant decrease of IL-2 and IL-3-LA after surgery may further explain the immunosuppression observed after operation.