Friday, October 31, 2008
Happy Halloween! It's time for creepy, crawly things that bite... and cause inflammation.
The brown recluse has the bite that keeps on giving. Its venom contains a phospholipase that cleaves membrane phospholipids to release arachidonic acid (omega-6 fatty acid precursor of inflammatory eicosanoids) and lysophosphotidylcholine that binds to multiple receptors to signal NFkB-based inflammation.
It’s Halloween and a time to talk about things that bite and sting. After all, the symbol of Halloween is the Jack-O-Lantern, the flame within, i.e. inflammation. Venom is Nature’s answer to the need for instant inflammation.
The brown recluse is adapted for hunting, killing and eating. The killing bite is the subject tonight. The recluse injects a venom designed to get the biggest bark for the bite. It uses the least amount of protein to immobilize its prey/meal. Of course, since spiders are suckers, it helps if the venom also liquifies its meal.
The venom also has a secondary use as a defense. In this case, if something too big to eat encounters a brown recluse, the goal is to encourage the big beast, you or me, to leave. No pain, no gain.
Venom provides a convergence of enhanced meal making and avoidance of being made into a meal. The answer is, of course, enzymatic inflammation. Venom contains enzymes that convert common cellular components into potent pyrogens, inflammation inducers. The wicked witch of the world of inflammation is phospholipase A2 (PLA2).
Brown recluse venom PLA2 clips off the arachidonic acid from membrane phospholipids and leaves an amphipathic detergent, lysophospholipid (LPL). The LPL can destabilize membranes and rupture cells. It is also a potent activator of several cell receptors that signal inflammation via NFkB. The COX-2 induced by inflammation has a readymade substrate present, arachadonic acid, and produces inflammatory prostaglandins, that continue the signaling frenzy. The result is inflammation, pain and necrosis.
Recluse bites are hard to treat. I think that some people recommend topical application of gunpowder. I guess that would make sense, because one of the problems of recluse bites is actually constriction of blood flow by other venom components, and nitroglycerin patches apparently provide some relief. Both the patches and nitrates of the gunpowder cause vasodilation, and would remedy some of the circulation problems of the venom. Glucocorticoids are also partially effective, since they are anti-inflammatory. Then there is heparin. I would always try heparin, at least as a last resort, because heparan sulfate proteoglycans are an essential component of most extracellular signaling systems, e.g. cytokines. Heparin should disrupt or activate all of these systems. It is unpredictable. It turns out that heparin is helpful against the brown recluse. I would also like to try a topical potion made of Vick’s Vaporub (menthol, eucalyptol, camphor, turpentine), castor oil and heparin. That should fix about anything. It even smells good, sooths painful joints and makes your skin soft.
Happy Halloween. Enjoy trick or treating, but watch where you put your hands.