The effect of omega-3 fatty acid status on lung inflammation in tuberculosis- infected mice

Abstract

Background: Tuberculosis (TB) bacilli successfully survive within the host. It causes an immune response that is defensive but also harmful to the host’s lung tissue, because of perpetuating inflammation. Non-resolving inflammation in TB persists and can occur in both latent and active TB. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have anti-inflammatory and inflammation-resolving activity due to their conversion to lipid mediators and influence on inflammatory cytokines. Aim: This project aimed to determine the effect of n-3 PUFA status prior to infection on lung inflammation and pathology in Mycobacterium tuberculosis (Mtb)-infected C3HeB/FeJ mice. Methods: Uninfected mice (n=20) were conditioned on either n-3 PUFA sufficient (n-3FAS) or deficient (n-3FAD) diets for six weeks and continued these diets post Mtb infection for an additional four weeks until euthanasia. Lung bacterial load, lung- and spleen-weight indexes and lung histology (free alveolar space), cytokines and lipid mediators were assessed. Results: The low n-3 PUFA status group (n-3FAD) had a trend to present with lower bacterial loads (p=0.095) and presented with lower spleen-weight indexes (p=0.041), more free alveolar space (p<0.001), lower pro-inflammatory lung cytokine concentrations (interleukin -1β, p=0.007; interleukin-6, p=0.003; interferon-gamma, p<0.001), and a less pro-resolving lipid mediator profile compared with the n-3FAS group (a trend for lower prostaglandin (PG) E3, p=0.068 and protectin D1, p=0.087; 18-hydroxyeicosapentaenoic acid, p=0.006 and 17-hydroxydocosahexaenoic acid, p=0.028; and higher PGE2, p=0.032). Conclusion: Contrary to what we hypothesized, if no drugs were administered, a low n-3 PUFA status prior to TB infection resulted in lower lung bacterial loads, and spleen body weight index, with a higher percentage lung free alveolar space and lower pro-inflammatory lung cytokine concentrations despite having a less pro-resolving lipid mediator profile.