Bee stings are far more common than people realise. Despite having never been stung myself, around 75% of Americans report being stung at least once in their lifetime, and there are an average 72 deaths annually in the US from hornet, wasp, and bee stings combined. Globally, around 3% of the world's population experience anaphylaxis in response to insect stings, with one of those people being Edmund Bridgerton from the beloved period drama. However, for the other 97%, bee stings mean nothing more than a few hours of swelling and localised pain.
So what is actually happening inside your body at a molecular level?
What Is Bee Venom?
Bee venom, or apitoxin, is a colourless acidic liquid made and secreted by worker honeybees. Each sting delivers about 50-100 micrograms into the victim, and the apitoxin consists of many proteins, enzymes, and peptides. The key components of apitoxin are:
1) Melittin - around 50% of the venom's dry weight and provides most of the pain associated with the sting
2) Phospholipase A2 - the enzyme that breaks down cell membranes
3) Histamines - this triggers rapid localised inflammation
4) Apamin - neurotoxic peptide that affects the nervous system
5) Adolpain - a peptide that inhibits the COX enzymes, which contributes to pain and also produces an anti-inflammatory effect
6) Hyaluronidase - an enzyme that breaks down the hyaluronic acid in connective tissue, facilitating the spread of toxins through tissue
When You Get Stung
A trait unique to bees is the fact that its barbed stinger continues to pump venom even after the bee has died (as the act of stinging tears apart the bee's abdomen).
Immediately after being stung, the first compounds to work are melittin and hyaluronidase. Hyaluronidase immediately starts to break down hyaluronic acid, which is a key structural component of connective tissue, and widens the space between cells. This creates pathways for the rest of the venom to spread through your tissue much more efficiently.
Meanwhile, melittin, an amphipathic (has both hydrophilic and hydrophobic regions) peptide, inserts itself directly into the phospholipid bilayer of the cell membrane. As a result, it disrupts the membrane of the phospholipid bilayer, causing the cells to leak and ultimately lyse. The destruction of the cell triggers the immediate sharp pain that signals to your immune system.
Inflammatory Response
Alongside melittin, phospholipase A2 acts as an enzyme that attacks the phospholipid molecules in the cell membrane, liberating a fatty acid called arachidonic acid which enters the cell and becomes the raw material for the inflammatory pathways that follow. Arachidonic acid is then converted by two enzyme families:
- COX enzymes produce prostaglandins, which sensitise pain receptors and promotes vasodilation, which causes the redness and heat around a sting
- LOX enzymes produce leukotrienes, which recruits immune cells to the site and contributes to swelling
While the rest of the venom is actively inflammation, adolapin simultaneously inhibits the COX enzymes. As a result, the venom partially suppresses its own inflammatory cascade at the same time as triggering it. This contradiction is one of the reasons why bee venom is difficult to study, but also why its therapeutic potential stays as an active area of research.
Immune System Response
Mast cells detect the foreign proteins in the venom and respond by releasing a flood of stored histamine into the surrounding tissue. The histamines bind to the receptors on nearby blood vessels, causing them to become more permeable. As fluid leaks out of the vessels and into surrounding tissue, the characteristic swelling and itching of a bee sting occurs. This is also why antihistamines like cetirizine can reduce these symptoms via blocking histamine receptors before histamines can bind to them.
So what should you do if you actually get stung?
1) Applying ice works as the cold temperature lowers the activity of enzymes (including PLA2 and hyaluronidase), as well as causing vasoconstriction. This reduces the rate at which inflammatory mediators spread through the tissue.
2) Removing the stinger quickly matters because the venom sac continues to contract and pump apitoxin into the skin for up to a minute post sting. The sooner it is removed, the less venom enters your body.
In the space of seconds, a microscopic droplet of apitoxin deploys a suite of specialised molecules that together disrupts cell membranes, spread through connective tissue, and activate inflammatory cascades.
Emily Jong