Publication date: 05-04-2012 11:12
This invention refers to the development of new formulations for anti-inflammatory therapeutic strategies.
While histamine is a well-described inflammatory mediator in allergic responses, its effects in brain immune responses remain scarcely studied. We have described a new role for histamine in the modulation of important microglial responses, such as cell motility and release of inflammatory mediators. Microglial cells are the resident immune cells in the brain and hold the ability to proliferate and migrate to the injury site where they produce/release several inflammatory mediators. We found that in a context of lipopolysaccharide (LPS)-induced inflammation, the activation of the histamine receptor 4 inhibits both microglia motility and the release of inflammatory molecules, contributing to the amelioration of the inflammatory status. To promote a more efficient and controlled delivery of histamine we used Poly(lactic acid-co-glycolic acid) microparticles loaded with histamine or histamine receptor agonists/antagonists. Microparticules are not cytotoxic and mimic completely the effects of histamine per se. Conceptually, histamine can act as an anti-inflammatory molecule by activating H4R, and therefore open new perspectives for the role of histamine which extends beyond the classical application of antihistamines. The findings reported in the present invention can be extended to novel applications concerning peripheral inflammation and anti-inflammatory activity of H4 receptor agonists in macrophages/monocytes and other immunity-competent cells.
|Data de prioridade||13-07-2011|
|Documento de patente|||