Omega-3 derivatives as a non-immunosuppressant alternative for COPD
Chronic obstructive pulmonar disease (COPD), mostly caused by years of smoking (although long-term exposure to lung irritants, such as polluted air, chemical fumes or dust, can also contribute), is principally characterised by inflammation and production of large amounts of mucus. In COPD, persistent airflow blockage can be due to one or more causes:
- Loss of bronchi and alveoli elasticity.
- Destruction of walls separating many of the alveoli.
- Bronchi walls becoming fat and inflamed.
- Bronchi producing more mucus than in normal conditions causing their obstruction.
In 2012, three million people died of the condition (6% of the total deaths registered that year).
COPD cannot be cured and giving up smoking is essential to preventing its progression, but there are therapies that can help control its symptoms (dyspnea, abnormal expectoration and chronic cough) and improve patients’ quality of life. The most common pharmacological therapy uses anti-inflammatory drugs, but because of their immunosuppressant effect, they can increase the risk of secondary infections, mostly nontypeable Haemophilus influenzae (NTHi), an opportunistic Gram-negative pathogen. These infections cause exacerbations that can threaten the lives of patients.
In murine models, NTHi is rapidly eliminated but a strong inflammatory response persists (indicating that NTHi induces deregulation of the normal inflammatory response and impedes resolution). Specialist pro-resolution lipid mediators play a critical role in actively resolving inflammation, reducing proinflammatory actions and favouring resolution pathways, without the iatrogenic immunosuppressant effects of classic anti-inflammatory therapies.
In a recent study, C57BL/6 mice treated with aspirin-triggered resolvin D1 (AT-RvD1) and infected with live NTHi had a lower total cell and neutrophil count in the bronchoalveolar lavage; they also showed a cytokine reduction 6 and 24 h post-infection and a lower NTHi bacterial load, despite the reduced inflammation. Furthermore, AT-RvD1 protected the NTHi-infected mice from weight loss, hypothermia, hypoxaemia and respiratory effects.
In other words, AT-RvD1 (derived from omega-3 polyunsaturated fatty acids) reduced lung inflammation in mice and eliminated the bacteria. These results highlight the beneficial effect of specialised lipid mediators in pulmonary bacterial infections and suggest they could be used as an alternative to immunosuppressant therapies..
- Croasdell A, Lacy SH, Thatcher TH et al. Resolvin D1 Dampens Pulmonary Inflammation and Promotes Clearance of Nontypeable Haemophilus influenzae. The Journal of Immunology. 2016; 196 (6): 2742-2752.
- National Institutes of Health. National Heart, Lung, and Blood Institute. What is COPD?
- Chronic obstructive pulmonary disease (COPD).Fact sheet. November 2016.