A New Way of Fighting the Flu
Since the resurfacing of H5N1 virus, more commonly known as bird flu, in Asia in 2003, the race to better understand – and fight – deadly influenzas has picked up pace. Influenza attacks the body in two ways – by killing lung cells outright, and by triggering an immune response that, when severe enough, can prevent the lungs from properly absorbing oxygen. The dangerous immune response hinges on the cellular release of small proteins called cytokines, which play a role in cell-cell interaction, communication, and behavior of other cells. These cytokines in turn recruit infection-fighting cells like immune T cells and macrophages to the infected site, often at dangerous levels.
A cytokine reaction can be severe enough to cause a “cytokine storm,” a condition in which the alveoli of the lungs become so flooded and clogged with the body’s own infection-fighting cells that they can no longer properly absorb oxygen. The ability to incite cytokine storms is what, in large part, makes certain epidemic strains of the flu so deadly. Permanent lung damage often results from a severe cytokine reaction, even if the patient survives.
Rather than seek to kill the virus itself, Scripps Research Professors Michael Oldstone and Hugh Rosen chose to focus on inhibiting the extreme cytokine response. By administering a compound known as sphingosine analog AAL-R directly to the lungs of mice, they found that the release of cytokines was greatly diminished, while the humoral immune response – the aspect of immunity in which plasma cells make viral antibodies – remained strong. This is the first time that scientists have been able to inhibit one aspect of the immune response while keeping another intact.
“Even though this compound does not kill the virus itself,” explains Oldstone, “the immunopathologic response was significantly impaired.” In order to lay the foundation for the best possible drug, the team plans to next study the basic mechanism for sphingosine analog AAL-R receptors. They also plan to look at combination therapy – adding Tamiflu to the drug treatment – as a way to both kill the virus and block the immunopathologic response.
With the threat of bird flu looming on the horizon, Oldstone and Rosen are in a race to uncover the deadly workings of epidemic viruses. So far, the strain has not mutated into a form easily transmitted between humans, but health officials fear that if it does a worldwide epidemic could result. The team’s research lays the groundwork for saving lives if such an epidemic were to occur. “Our hope is that our current research will yield answers about how to treat this kind of immune response not only in influenza, but also in other viral diseases such as hantavirus and SARS in which pulmonary infiltration is severe,” explains Oldstone.
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