Therapeutic Exploitation of Endogenous Anti-Inflammatory Mechanisms:Old and New Leads

D.      Renshaw; P.      Urquhart; M.      Perretti

Abstract

Understanding the way our body switches off host defence responses has yielded some of the most innovative recent discoveries in inflammation research. In reality the concept is not new, and was already implicit in early publications of the 1970s which showed that during inflammation, glucocorticoids are increased in the circulation and that these protect the host from over-shooting and ensuing self-inflicted injury. Stemming from the first example of drugs developed on an endogenous anti-inflammatory pathway, that of the glucocorticoid, we have here touched upon other counterregulatory breakpoints, such as those centred on melanocortins; the annexin 1 system; the polyunsaturated fatty acid derivatives lipoxins and resolvins; galectin-1 and selected others, including novel chemical entities engineered to release anti-inflammatory gases and factors originally discovered in the developmental field. We propose that understanding the molecular mechanisms switched on by a given anti-inflammatory mediator and the events it modulates in target cells will be of great help in developing innovative ways to control inflammatory pathologies. This seems quite articulated and with a degree of complexity in the group of developmental axonal guidance factors. We propose that drugs discovered along this philosophy will have a better compliance and would be theoretically devoid of side effects since they will be acting by mimicking the way our own body assures the inflammatory response is restricted both spatially and temporally.

Keywords: Glucocorticoids, anti-inflammation, lipocortin 1, neutrophil, melanocortins, galectin-1, lipoxins, resolvins