Peptide Therapy Reduces Lung Inflammation

A team of immunologists used a peptide to block the activity of the inflammatory protein nuclear factor-kappa-B (NF-kappa-B), which strikingly reduced the level of lung inflammation caused by infection with methicillin-resistant Staphylococcus aureus (MRSA).

Acute lung inflammation is a potentially life-threatening complication of infections due to community-acquired methicillin-resistant S. aureus, a worldwide emerging pathogen, which causes necrotizing pneumonia and acute respiratory distress syndrome (ARDS).

To counter the damage done to the lungs by MRSA, investigators from Vanderbilt University Medical Center (Nashville, TN, USA) designed a peptide to mimic the signal that orders NF-kappa-B to travel from the cell's cytoplasm to the nucleus.

The scientists reported in the March 3, 2009, online edition of the journal Molecular Therapy that in a mouse model the "nuclear import inhibitor” of NF-kappa-B suppressed production of a wide spectrum of cytokines and chemokines induced by direct staphylococcal enterotoxin B airway exposure. Consequently, trafficking of neutrophils, monocytes/macrophages, and lymphocytes to the bronchoalveolar space was significantly reduced while vascular injury, manifested by increased permeability and protein leakage, was attenuated.

"To our delight, we found that this peptide crossed the cell membrane and stopped NF-kappa-B in its tracks, blocking it from going to the nucleus in response to conditions, which cause inflammation,” said senior author Dr. Jacek Hawiger, professor of microbiology and immunology at the Vanderbilt University Medical Center. "We believe that in addition to controlling the infection with antibacterial and antiviral agents, we need therapies that reduce this inflammation-induced collateral damage to the lung tissue. This would allow both faster clearance of the infecting organisms and faster healing of the lung.”

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Vanderbilt University Medical Center