The immunomodulatory effect of Apis mellifera bee venom on the cytokines level in spleen of BALB/c mice

Abstract

Bees are like other animals; they defend themselves against threats and predators because of their venomous sting. Their venom can cause sudden pain at the site of the sting leading to swelling, redness, itching and localized heat. Bee venom contains a complex mixture of peptides, toxic proteins, enzymes and other bioactive components. The main enzymes present are phospholipase A, hyaluronidase, and lecithinase. Although the bee venom is considered cytotoxic, it possesses many beneficial effects and has been used in different oriental medicinal therapies as biomarkers to treat plenty of human inflammatory diseases. A.mellifera syriaca belongs to the bee family of Apis mellifera. It is the endemic honey bee subspecies present in the Middle East mainly in Syria, Lebanon, Jordan, Iraq and Palestine. Biological characteristics of this venom revealed that it exhibits anti-microbial, anti-cancerous, and antioxidant activities in vitro. This study investigates the study the immunomodulatory effect of the honey bee venom A. mellifera syriaca on mice in vivo for the first time on the murine splenic levels of both pro and anti-inflammatory cytokines TNF α, IFN γ, IL-4 and IL-10. BALB/c mice were injected intraperitoneally with different doses of venom in order to calculate the median lethal dose of the venom. After 24 hours, LD50 of A. mellifera was proved to be equal to 3 mg/kg in our experimental conditions. Quantitative measurement of cytokines was assessed using ELISA kits. As compared to the control, the three different doses of venom (1 mg/kg, 2 mg/kg and 3 mg/kg) modulated the levels of cytokines along a different time course (6 and 24 hours post injection). In general, A. mellifera venom is shown to increase anti-inflammatory cytokines and decrease the pro inflammatory cytokines. Thus, the venom has anti-inflammatory potential that can defend against tumor and autoimmune diseases and thus potentially be a novel therapeutic in the growing field of cancer immunotherapy as well as other diseases such as Rheumatoid Arthritis.