Preclinical and early stage clinical study on the regulation of tumor-associated inflammatory factor IL-6 by traditional Chinese medicine compound formula BDL.

Abstract

e15131 Background: IL-6 has been found to be highly expressed in a wide range of cancer species and is thought to be associated with poor prognosis and treatment resistance. IL-6 inhibitors like tocilizumab are used to treat inflammatory diseases and cytokine release syndrome. We hope to find effective drugs in traditional Chinese medicine to improve patients' conditions with oral taking, lower price and longer lasting effect. BDL is a formula made up of 7 traditional Chinese medicines and has been used for years to boost immunity and anti-inflammatory treatment. We have previously confirmed that BDL can inhibit IL-6 in tumor cells in vitro and animal experiments. This study aims to clarify the toxicological effect of BDL granules and explore the effectiveness and safety in reducing the level of IL-6 in cancer patients in clinical practice. Methods: The content and active ingredients of BDL granules were determined by high performance liquid chromatography (HPLC). SD rats were gastric perfused with BDL, single dose toxicity study and 4 weeks repeat dose toxicity study were performed respectively. General behavioral, hematological and blood biochemical parameters and histopathology were observed and recorded. The clinical study included 25 cancer patients with elevated IL-6 who were given BDL granules orally, 48g per day, twice for 7 consecutive days. The changes of serum IL-6 levels were detected before and after medication. Results: The traditional Chinese medicines used to prepare BDL granules include Rhubarb, Radix Isatidis and Cornus officinalis. The quality of the main active ingredients such as emodin, chrysophanol, (R.S)–geichenol, maggianin were analyzed and controlled according to the requirements of Chinese Pharmacopoeia. BDL was found non-toxic up to 24g/kg in single-dose study, and the safe dose of BDL for rats after 4 weeks was 12g/kg, which was much higher than the applied concentration on human (0.8g/kg). All the animals survived to the end of the experiment, gross pathology, blood chemistry, hematology and histopathology were within normal ranges. Among the 25 enrolled patients, 76% had lower IL-6 levels after medication than before, and the difference was statistically significant (* P < 0.05). Treatment-related adverse reactions included abdominal pain (4%) and diarrhea (12%), among which 1 case of grade 3 diarrhea was relieved after symptomatic treatment. No hematological and biochemical toxicity was found. Conclusions: BDL granules meet China's national good manufacturing practices (GMP) standards and reduce IL-6 levels in cancer patients, which is safe and effective, may be considered for the treatment of tumor-related inflammation, reduce the inflammatory side effects caused by immunotherapy and improve the prognosis of tumor patients in combination with other drugs. Further clinical research is still needed.