乌鸦传媒

AMSTERDAM -- An investigational inhaled drug for chronic obstructive pulmonary disease (COPD) inhibited neutrophil enhancement and inflammatory cytokine release in a small clinical study, a researcher reported here.

The drug in question, still undergoing clinical trials, is known as AZD7624 (or simply 7624), an inhaled p38 inhibitor developed by AstraZeneca. The drug appeared to show promise for its anti-inflammatory properties when it was tested using lung and systemic markers of inflammation following a lipopolysaccharide (LPS) challenge.

"The anti-inflammatory potential indicates 7624 as a novel treatment for COPD," said lead study author , a research scientist at AstraZeneca, the drug's manufacturer. "We can dampen some of the inflammation of COPD, but more remains to be seen in follow-up studies."

Patel presented the findings at the International Congress.

Patel and colleagues randomized 30 healthy volunteers in a . Participants received a single inhaled dose of AZD7624 (1200 micrograms) or placebo 30 minutes prior to undergoing an LPS challenge, a test designed to trigger the body's inflammatory response mechanisms. Sputum induction followed 6 hours after the LPS challenge, and blood samples were taken at 0.25, 6.5, 12, and 24 hours post-dose in order to measure cell counts and inflammatory biomarkers.

The research team found that inhaled AZD7624 reduced LPS challenge-induced inflammation in both sputum and blood, attenuating a sputum neutrophil differential increase of 56.8% (P<0.001) compared with the placebo. This reduction, Patel noted during his presentation, is more than twice that of other p38 inhibitors. The target is mitogen-activated protein kinase long recognized for its pro-inflammatory properties.

During the study, AZD7624 also mitigated an increase of interleukin-6, an inflammatory cytokine, in the sputum by 76.5%, and led to attenuated differential increases of blood neutrophil counts by 43.5% and blood interleukin-6 by 70%.

Perhaps most tellingly, however, AZD7624 completely inhibited the macrophage inflammatory protein known as MIP-1β or CCL4, in the blood. AZD7624 also attenuated the degree of C-reactive protein increase by 93% in the blood following the LPS challenge.

There also was a significant change in sputum neutrophilia and interleukin 6, correlated with change in blood neutrophilia (R=0.531, P<0.0001) and interleukin-6 (R=0.492, P=0.0003).

As a result of the findings, the study authors concluded, "inhaled AZD7624 significantly inhibits LPS-induced lung and systemic inflammation, and lung inflammation markers correlate with systemic markers indicating a potential for AZD7624 as an inhaled treatment for COPD."

Though the study was a big first step, Patel said the research team is continuing to work to answer more questions about the drug.

Patel and other AstraZeneca officials are currently recruiting participants for a to investigate the efficacy and safety of AZD7624 in COPD patients who are on standard maintenance therapy.

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