Keep up the good work, Sharon!
For anyone looking at Dr. Fedson's research, just remember that it can be dangerous to take statins at the same time as fibrates:
Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza
We have shown that gemfibrozil, when administered i.p. on days 4 to 10 after exposure to virus, after the onset of illness, significantly increased survival in mice with severe influenza.
Although gemfibrozil is as yet untried in human influenza, it could have two major advantages. First, it is already approved for daily human use, albeit by a different route, to lower plasma lipids and cholesterol (18, 23). Second, from our data, enhanced survival did not depend on giving gemfibrozil before the onset of illness, since treatment begun 4 days after exposure to virus, when mice were already sick and had lost weight, was effective. This implies that gemfibrozil has the potential to be a treatment rather than a preventative in human disease, allowing limited stocks of the drug to be focused where required in a pandemic. The idea that severe systemic inflammatory disease arises through overproduction of proinflammatory cytokines in influenza (6, 8) now also has general acceptance. This made it attractive to test the effects of gemfibrozil on influenza, a disease acknowledged to operate through these cytokines. No fibrate appears to have been previously tested against an infectious disease.
Using anti-inflammatory agents against influenza is a recent suggestion, with Fedson proposing statins as a prophylaxis and treatment for an influenza pandemic (11, 12). While the concept has been gaining favor (20), no direct data are as yet available. Since the aim of this study was to find an agent useful in animals already sick from influenza, our initial trials included simvastatin at the human daily maintenance dose for lowering blood lipids. Unlike gemfibrozil, simvastatin had a negligible effect on sick animals under these conditions. Nevertheless, the use of statins in influenza, including as prophylactic agents, warrants closer examination, since the epidemiological data that support the protective effects of statins arose from sepsis patients who were already taking these drugs at the time they became ill (1).
We also found that gemfibrozil gave some protection, in survival terms, against the severe systemic inflammatory illness that results from administering LPS (Fig. 3). This suggests that it could also protect against other similar inflammatory conditions as well as influenza. In addition, activity against LPS implies that at least a major effect of gemfibrozil against influenza is to inhibit inflammatory cytokines, not the virus. Nevertheless, the mechanisms by which gemfibrozil exerts the effects we have observed are yet to be elucidated. Our next priorities are to examine whether inflammatory cytokine production is inhibited and to determine if gemfibrozil has any direct antiviral action.
Although the published mouse 50% lethal dose of gemfibrozil is 3,162 mg/kg for a single orally administered dose, and 300 mg/kg/day of gemfibrozil, given for 3 or 12 months, is well tolerated in rats (15), we are wary of extrapolating this to pathogen-infected mice without further study. Also, it is yet to be ascertained how outcomes of oral and i.p. dosages compare. As noted elsewhere (3), gemfibrozil reduces the production of inflammatory cytokines, molecules that are involved in the host response against pathogens as well as disease pathophysiology (6). The literature on the effects of anti-TNF agents in rheumatoid arthritis provides an example of this useful and harmful duality of inflammatory cytokines (22). This possibility in influenza will be examined in several ways, including further parallel studies using gemfibrozil against influenza and LPS toxicity. The LPS model is useful because it involves no cytokine-susceptible infectious agent and causes pathology only through excessive cytokine production.
In summary, if these results translate to human infections, gemfibrozil may prove to be a readily testable and useful treatment for influenza, both in high-risk individuals with the currently circulating influenza virus strain and in any pandemic resulting from an antigenic shift in a subtype, including the current avian H5N1 influenza virus.