Neutrophil generation of inflammatory precursors is not modulated by docosahexaenoic acid

It is believed that correction of membrane fatty acid deficiency in cystic fibrosis (CF) downregulates the synthesis of proinflammatory mediators. We tested the hypothesis that an increase of the proportion of docosahexaenoic acid (DHA) in the membrane in vitro changes the neutrophil response to Pseudomonas aeruginosa lipopolysaccharide (LPS). Treatment with DHA increased the secretion of interleukin(IL)-1|*alpha*| by CF neutrophils, but the secretion of other cytokines, CD11b expression, and arachidonic acid (AA) release were not affected either in CF or control (CT) neutrophils. Both with and without DHA, only one out of eight CF neutrophils responded to LPS with an increase of released AA, while five out of seven CT cells released more AA (CF vs. CT P < 0.05 by Fisher test). These results indicate that in neutrophils the beneficial effects of DHA on immune response are not directly related to the generation of proinflammatory precursors, and suggest that in CF the lower neutrophil AA generation in response to activation could cause insufficient production of lipid mediators involved in the resolution of lung inflammation

Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation

High amounts of glutamate are found in the brains of people with multiple sclerosis, an inflammatory disease marked by progressive demyelination. Glutamate might affect neuroinflammation via effects on immune cells. Knockout mice lacking metabotropic glutamate receptor-4 (mGluR4) were markedly vulnerable to experimental autoimmune encephalomyelitis (EAE, a mouse model of multiple sclerosis) and developed responses dominated by interleukin-17-producing T helper (T(H)17) cells. In dendritic cells (DCs) from those mice, defective mGluR4 signaling-which would normally decrease intracellular cAMP formation-biased T(H) cell commitment to the T(H)17 phenotype. In wild-type mice, mGluR4 was constitutively expressed in all peripheral DCs, and this expression increased after cell activation. Treatment of wild-type mice with a selective mGluR4 enhancer increased EAE resistance via regulatory T (T(reg)) cells. The high amounts of glutamate in neuroinflammation might reflect a counterregulatory mechanism that is protective in nature and might be harnessed therapeutically for restricting immunopathology in multiple sclerosis