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Clinical trials of Ebola treatment to start in Africa

BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g5838 (Published 23 September 2014) Cite this as: BMJ 2014;349:g5838

Re: Clinical trials of Ebola treatment to start in Africa

Although direct antiviral treatments through passive immunity would certainly have potential for treating Ebola, it’s not the virus which kills, but rather the damaged immune system discharging a “cytokine storm” and large amounts of nitric oxide, damaging blood vessels, causing blood and plasma leakage and dangerously low blood pressure similar to severe septic shock (1).

Treatment with melatonin might have some potential for alleviating the morbidity and mortality of Ebola virus infection, since melatonin has immuno-modulating and inhibitory functions against production and activation of pro-inflammatory mediators such as cytokines as well as preventing multiple organ and circulatory failure in septic shock and also has antiviral actions (2).

Ebola also causes coagulation abnormalities leading to hemorrhage through dramatically increased levels of tissue factor from lymphoid macrophages (3).

Melatonin stimulates release of a tissue factor pathway inhibitor from the vascular endothelium, which could potentially reduce bleeding complications from excessive tissue factor release (4).

Since melatonin has virtually no toxicity, along with conventional therapy (5), it would appear to have potential for treatment of ebola viral infection, to reduce complications such as organ failure, bleeding and shock, and possibly could reduce the mortality rate.

References:

1. http://www.npr.org/blogs/goatsandsoda/2014/08/26/342451672/how-ebola-kil...

2. Srinivasan V, Mohamed M, Kato H. Melatonin in bacterial and viral infections with focus on sepsis: a review. Recent Pat Endocr Metab Immune Drug Discov. 2012; 6: 30-39.

3. Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis 2003; 188: 1618-1629.

4. Kostovski E, Dahm AE, Iversen N, Hieltnes N, Osterud B, Sandset PM, Iversen PO. Melatonin stimulates release of tissue factor pathway inhibitor from the vascular endothelium. Blood Coagul Fibrinolysis. 2011; 22: 254-259.

5. Escames G, Acuna-Castroveijo D, Lopez LC, Tan DX, Maldonado MD, Sanchez-Hidalgo M, Leon J, Reiter RJ. Pharmacological utility of melatonin in the treatment of septic shock: experimental and clinical evidence. J Pharm Pharmacol. 2006; 58: 1153-1165.

Competing interests: No competing interests

25 September 2014
Steven R Brenner
Physician, semi-retired.
Saint Louis University Department of Neurology and Psychiatry
Department of Neurology & Psychiatry, Saint Louis University School of Medicine, Monteleone Hall, 1438 South Grand Blvd., St. Louis, Missouri 63104