The pharmaceutical industry has long been attempting to develop a means by which interference with cholesterol production might be achieved farther along the biosynthetic pathway, beyond the point where vital intermediary products such as ubiquinones and dolichols originate but up to now, has failed.
Even greater challenges exist to drug company scientists from the recent findings that suggest statins work not by cholesterol manipulation but by some basic anti-inflammatory role. Key to this is a substance known as nuclear factor kappa B. All statins inhibit this vital step in the immuno-defense system. Statin drugs are known to suppress this nuclear factor kappa B (NF-kB) response and thereby open a veritable Pandora's box of unpredictable consequences.
It is in the nucleus of the cell that NF-kB completes its mission in life to stimulate genes and manufacture proteins necessary for such diverse tasks as monocyte adhesion, macrophage recruitment, smooth muscle migration and platelet activation, key elements of the defensive inflammatory response.So what of statin drugs now well-established effect of inhibition of NF-kB? What does this really mean in the ancient struggle with disease organisms and the immune system's competence? The reality is that we do not as yet know because this new statin role of NF-kB inhibition has only just been recognized.
The implications of the very recent drug company promotion of statin drugs for organ transplant recipients and as adjunctive therapy in the treatment of auto-immune diseases are sobering, indeed, for these drugs can only work in this capacity at the risk of causing mischief elsewhere.
How strange it is that a class of drugs developed solely for the purpose to interfering with the biosynthesis of cholesterol has now been shown to reduce cardiovascular risk by an anti-inflammatory role completely unrelated to cholesterol manipulation.
Generally speaking this should by a welcome observation, for atherosclerosis with all of its consequences appears to be based primarily upon inflammation within the arterial walls. Now, however, any optimism we might have had is thoroughly tempered by the growing realization that the statins' effect is based upon interference with our most basic immuno defense system. The potential consequences are frightening.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor