Tag Archives: cytokine

Ekybion: Inhibitor of influenza or immune-response?

Contributed by Guest Blogger: H. Cushing ’14

Ekybion is a drug complex that was developed to treat inflammation in the respiratory tract caused by infectious agents. A series of experiments were implemented to test if Ekybion was capable of inhibiting the growth of influenza A/PR/8/34 H1N1 strain in vivo (mice).
The first experiment was performed in vitro. MDCK cells were treated with Ekybion 1 hour pre-infection, 1, 2, 4, or 12 hours post-infection. Samples of the different cultures were taken 24 and 48 hours after infection and the number of influenza viruses were counted using the hemagglutination assay method. The results showed that the treatment of MDCK cells (whether pre/post infection) significantly reduced viral growth for at least 48 hours and that pre-infection treatment was most efficient.
The first experiment done in vivo was testing the possible toxicity of Ekybion. They treated one of two groups of mice three times a day with Ekybion. The toxicity was determined by the mice’s weight and normalcy of lung tissue. The test was done with several different concentrations of Ekybion. The results showed that no toxicity was observed in the treated mice until 50x concentration level was reached – indicating that no toxicity would result from Ekybion use at 1x (concentration intended for medical use).
Ekybion’s inhibition of the virus in infected mice was tested at different treatment times and concentrations. Mice were weighted daily for 16 days and 2-5 mice were euthanized from each group on the second day post-infection to determine the amount of virus in lung tissue. The results showed no significant differences in weight loss and that the treatment with 1x concentration for 2 minutes was the most effective with a 46% survival rate (compared to 0% survival in the control). The lung tissues collected from the euthanized mice were used to determine cytokine levels at the site of infection. The results showed that mice treated with Ekybion had a lower cytokine quantity. This determined that Ekybion could suppress immune response as well as reduce viral growth. The question resulting from the experiments is whether or not the anti-viral benefits outweigh the immunosuppression effect of the drug.


A cure for cold sores?

ContribUted by Guest Blogger: A. Parayannilam ’13

The cold sores many of us see on our mouths or faces at one point in our lifetimes are caused by the prevalent Herpes simplex virus Type 1(HSV1). More serious symptoms can develop if the virus infects the Central Nervous System, causing herpes encephalitis and damage to the brain. A recent study has shown how interferon delta (IFN-λ), a member of a group of proteins known as interferons (IFNs), can reduce infectivity of the virus in the Central Nervous System. The results of the study are promising: perhaps by recruiting the body’s own defenses, we can avoid the use of potentially unsafe antiviral drugs in treatment for the disease.
Researchers observed IFN-λ to significantly reduce the quantity of the virus found in infected cells of the central nervous system, specifically astrocytes and neurons. Researchers investigated the mechanism behind IFN-λ’s anti-HSV-1 effect and found that IFN-λ activated several Type 1 IFNs. Type 1 IFNs play critical roles in our innate immunity and defense against viruses. To test the significance of Type 1 IFNs, researchers treated astrocytes and neurons with Type 1 IFN antibodies, essentially preventing IFN- λ from activating Type 1 IFNs in these cells. The antibody-treated cells became highly susceptible to infection, highlighting the importance of Type 1 IFNs in the virulence of the disease.
Another method by which IFN- λ reduces infectivity of the virus is by promoting cytokine signaling. Cytokine signaling is a method of intercellular communication cells use to warn each other of infection. Because HSV-1 suppresses cytokine signaling, uninfected cells aren’t able to prepare themselves for possible infection, making these cells more susceptible to infection.
The study raises a number of questions. The researchers discuss the interplay between HSV-1 and interferon delta, but how about the interplay between HSV-2 and interferon delta? The study examines how interferon delta can reduce infectivity in astrocytes and neurons– can interferon delta similarly reduce infectivity in cells outside the Central Nervous System? Is this a fix to the annoying, chronic cold sores that affect the majority of us?