Inhibition of systemic TNF-alpha cytotoxicity in cancer patients by D-peptidoglycan.

The current study was designed to investigate direct inhibitory effects of N-acetyl-glucosaminyl-muramyldipeptide (GMDP) over the cytotoxic nature of TNF-alpha. A lactate dehydrogenase (LDH) assay of the inhibition of TNF-alpha cytotoxicity was done in vitro on the following cell lines: A549 (human lung carcinoma cells), A431 (human breast cancer cells) and L929 (mouse breast cancer cells). In a double-blind placebo-controlled trial, cancer patients with an elevated activity of all five LDH isoensymes were randomized to receive either a GMDP solution or a placebo; 63 patients were evaluated every third day for the mean daily number of episodes of nausea or vomiting, changes in clinical status, cell blood count and blood chemistry. A 95% inhibition of LDH release was noticed on A549 cells. Other cell lines were less sensitive to GMDP, with an observed 72% dose-dependent reduction in LDH activity. In vivo, LDH activity was decreased by 41% (+/-4%) (mean+/-SD) in all 21 subjects who were given 0.5-1.0 mg of GMDP daily. A lowering of LDH activity by 73.4% (+/-4%) was observed in 23 patients who received GMDP at a dosage of 1.5mg/kg daily. Correspondingly, a 10% (+/-2%) increase in LDH activity was noticed in 19 patients who were given a placebo (P < 0.01). During the follow-up period, the overall clinical condition of all patients treated with GMDP was improved. No side effects were observed. In nine patients who experienced nausea from tumor toxicity before treatment, the symptom subsided. In parallel, an extremely beneficial effect on lipids metabolism was noticed in all patients with elevated cholesterol and trigliceride levels. A dietary supplementation of GMDP has been shown to reduce systemic TNF-alpha cytotoxicity during tumor shock.