Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9008247 | International Immunopharmacology | 2005 | 10 Pages |
Abstract
As part of a program researching the synthesis and immunopharmacological evaluation of novel synthetic compounds, we have described the immune modulatory profile of the new achiral thalidomide analogue LASSBio-468 in the present work. This compound was planned as an N-substituted phthalimide derivate, structurally designed as a hybrid of thalidomide and aryl sulfonamides, which were previously described as tumor necrosis factor-alpha (TNF-α) and PDE4 inhibitors. LASSBio-468 was recently demonstrated to inhibit the TNF-α production induced by lipopolysaccharide (LPS), in vivo. Here, we investigated whether this compound would affect chronic inflammation processes associated with the production of this pro-inflammatory cytokine. Treatment with LASSBio-468 before a lethal dose injection of LPS in animals greatly inhibited endotoxic shock. This effect seems to be mediated by a specific down regulation of TNF-α and nitric oxide production, regulated mainly at the RNA level. In another model, histopathological analysis indicated that this compound also inhibited adjuvant-induced arthritis in rats. Taken together, our data demonstrated a potent anti-inflammatory effect of LASSBio-468, suggesting its use as a potential drug against chronic inflammatory diseases.
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Immunology
Authors
Magna S. Alexandre-Moreira, Christina M. Takiya, Luciana B. de Arruda, Bernardo Pascarelli, Raquel N. Gomes, Hugo C. Castro Faria Neto, LÃdia M. Lima, Eliezer J. Barreiro,