Lokesh Sharma, Ph.D.

Lokesh Sharma, Ph.D.

Institution: Yale University

Project: Mechanisms of Paradoxical Anti-inflammatory Effects of Type I Interferons in the Lung

Grant(s): Catalyst Award

Lung diseases are a leading cause of death worldwide and the fourth leading cause of death in the United States. Lung diseases manifest as both acute lung diseases, such as pneumonia, or as chronic diseases, such as idiopathic pulmonary fibrosis or chronic obstructive pulmonary disease. In both acute and chronic lung diseases, inflammation plays a key role in either onset or progression of the disease. However, the conventional anti-inflammatory therapies such as steroids have not been very effective against these lung diseases. We have found that proteins called type I interferons limit inflammation in the lung in three independent models of non-viral inflammation. We will identify the lung cell that contributes to this effect as well as determine the mechanisms that contribute to the anti-inflammatory effects of type I interferons. We also aim to boost this anti-inflammatory process to improve outcomes of lung disease.

Supported by the Mary Fuller Russell Fund

Update:

We have demonstrated that a critical role of type I interferon is protecting patients from a severe disease, hospitalization, and death. Given a well-established protective role of type I interferons against a broad range of viral infections, this study suggests that type I interferons can serve as an important therapeutic agent where virus-specific pharmacological approaches are not available. This can provide an essential therapeutic application for novel emerging viruses that are not well-characterized, and the development of target therapies can take years to come.

In another study supported by the American Lung Association, we found that early inflammatory response was essential in COVID-19 patients who were diagnosed before the onset of symptomatic disease. We found that patients who could mount a robust early inflammatory response were more able to prevent the onset of symptoms. These patients were young and were able to mount an immune response in a timely manner. These studies provide important insights into the perils of using anti-inflammatory therapies during early infection.

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