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Abstract
The venom of Apis mellifera (honey bee) has been reported to play a role in immunotherapy, but existing evidence to support its immuno-modulatory claims is insufficient. Four fractions from whole bee venom (BV) were separated using medium pressure liquid chromatography. Their ability to induce the production of cytokines TNFα, IL-1β and IL-6 in phorbol-12-myristate-13-acetate (PMA)-treated U937 cells was assessed. The levels of the three cytokines produced by stimulation with the four fractions and crude BV without LPS were not significantly different from negative control values. However, co-stimulation of the cells with LPS and Fraction 4 (F-4) induced a 1.6-fold increase in TNF-α level (p < 0.05) compared to LPS alone. Likewise, LPS-induced IL-1β production was significantly synergised in the presence of F-1 (nine-fold), F-2 (six-fold), F-3 (four-fold) and F-4 (two-fold) fractions, but was only slightly enhanced with crude BV (1.5-fold) relative to LPS. Furthermore, the LPS-stimulated production of IL-6 was not significantly increased in cells co-treated with F-2 and F-3, but the organic fraction (F-4) showed an inhibitory effect (p < 0.05) on IL-6 production. The latter was elucidated by NMR spectroscopy and found to contain(Z)-9-eicosen-1-ol. The effects observed with the purified BV fractions were more marked than those obtained with the crude sample.
Highlights
Bee venom (BV) is mainly used as a defence tool by the honey bee, and its primary function is to inflict pain on any intruders into the hive [1]
Melittin was the principal component of F-3 (96% purity) (Figure S12), while the organic fraction, Fraction 4 (F-4), mainly contained a new compound identified through NMR analysis as (Z)-9-eicosen-1-ol and trace levels of an unidentified phospholipid
The largest synergistic effect was observed for IL-1β release, which was promoted by all fractions, while only the lipid fraction, F-4, enhanced tumour necrosis factor (TNF)-α production in the cells co-stimulated with LPS
Summary
Bee venom (BV) is mainly used as a defence tool by the honey bee, and its primary function is to inflict pain on any intruders into the hive [1]. Despite its pain-causing effects, the main reported human administration uses relate to pain relief in conditions, such as arthritis and rheumatism [2,3], tendonitis, multiple sclerosis, wounds and gout [4,5,6]. 50%–60% of the venom by dry weight and is responsible for most of the observed effects [9,11,12]. BV components have been reported to possess various and, sometimes, conflicting immune-related effects. Available evidence suggests that apamin [13], histamine [14], mast cell degranulating (MCD) peptide [15,16] and phospholipase A2 (PLA2 ) [17] significantly increase the inflammatory response. The small neurotoxic peptide apamin (MW 2.0 kDa) is a Ca2+ -activated
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