A Biological Study on the Efficacy of Low–Dose Subcutaneous lnterleukin–2 plus Melatonin in the Treatment of Cancer–Related Thrombocytopenia

Abstract

The production of cytokines involved in platelet generation, including inter-leukin (IL)-3, IL-6 and IL-11, is stimulated by IL-2. However, the platelet number has been shown to decrease on IL-2 cancer therapy, and this side effect depends on the enhanced peripheral platelet destruction following the activation of the macrophage system by IL-2 itself. Our previous studies showed that IL-2-induced macrophage activation may be counteracted by the pineal hormone melatonin (MLT). On this basis, a pilot study with IL-2 plus MLT was performed to evaluate its influence on the platelet number in cancer patients with persistent thrombocytopenia. The study included 20 advanced solid tumor patients, who received IL-2 at 3 million IU/day s.c. for 6 days/ week for 4 weeks in association with MLT (40 mg/day orally). A normalization of the platelet number was achieved in 14/20 (70%) patients. This pilot study shows that the therapy with low-dose IL-2 plus MLT, in addition to its previously described antitumor activity, may also be effective in the treatment of cancer-related thrombocytopenia.

The Effects of Melatonin on Angiogenesis and Wound Healing

“…Pineal melatonin augments the antitumor activity of IL-2, prolongs survival, and reverses thrombocytopenia. [22][23][24] Melatonin in the bone marrow has a high level of affinity to T-helper type lymphocytes. The activation of melatonin receptors increases the pro- …”

H-NMR and FT-IR study of the state of melatonin confined in membrane models: location and interactions of melatonin in water free lecithin and AOT reversed micelles

“…At muscular level they damage and destroy membranes, disarm enzymes, and alter the genetic map; all these effects occur in a very short time (about 1 ns). In absence of anti-oxidant agents, their action is devastating and relentless 4 determining irreversible chemical changes and could lead to a series of diseases such as cancer, 5,6 AIDS, 7 cataract 8 and cardiac, 9 Parkinson's and Alzheimer's 10,11 diseases. MLT is resulted five times more effective than glutathione in capturing hydroxyl radicals and five hundreds times more effective than dimethyl sulfoxide in safeguarding chromosomes from radiation induced damages.…”

Melatonin and the Immune System

“…In human breast cancer [20][21][22][23][24] and prostate cancer patients [25,26] dy namic changes o f melatonin synthesis were described dur ing different phases o f disease, with an initial stimulation at very early stages, a subsequent decline in parallel to the growth o f the primary tumor, and a restimulation as second ary growth arises. Liebmann/Wölfler/Felsner/Hofer/ Schauenstein Furthermore, melatonin was reported to reduce the tu mor growth in human patients suffering from advanced lung or colorectal cancer or brain metastases [27], to potentiate the therapeutic effect o f interleukin 2 (IL-2) treatment [28,29], and to protect against the negative side effects o f IL-2 treatment in non-small cell lung cancer [30], The possible clinical relevance o f melatonin in neoplastic diseases was recently reviewed by Webb and Puig-Domingo [31]. The mechanism o f action o f melatonin against tumor growth in vivo is multifactorial, and may partially lie in stimulatory effects on immune functions [32], It was recently shown that a 30-day melatonin treatment in patients with advanced solid tumors led to increased serum levels o f circulating tu mor necrosis factor-a, IL-2, and y-interferon (y-IFN) by 28, 51, and 41%, respectively, as compared with pretreatment levels [33].…”