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InflammoPharmacology

, Volume 10, Issue 3, pp 159–171 | Cite as

Pharmacological implications in the switch from acute to chronic inflammation

  • Franco Dallegri
  • Luciano Ottonello
Article

Abstract

Resolution or persistence of the inflammatory response strictly reflects the dynamic balance between two major determinants: (1) the recruitment of circulating inflammatory cells together with the proliferation of resident cells and (2) the death, or apoptosis, of cells accumulated locally. The link between these two determinants seems to be represented by the incapacity of monocytes and macrophages to switch off activation of inflammation, thereby acting as a major promoter of the inappropriate recruitment, retention and survival of activated cells at inflamed tissue sites. Various pathways contribute to the persistent macrophage activation and, therefore, represent major rational targets for biologic approaches aimed at controlling the evolution of inflammation. These pathways include the continuous recruitment of Th1 cells into inflamed tissues, the subnormal production of anti-inflammatory IL-10 by regulatory T cells and macrophages, the reduced release of adenosine by endothelial cells and fibroblasts, the reduced production of soluble decoy receptors for TNF by macrophages and the reduced local availability of the anti-inflammatory cytokine IL-1 receptor antagonist. Moreover, the persistent activation and the survival of inflammatory cells strictly depends on the activity of the NF-κB system, which is responsible for inducing the synthesis of proinflammatory mediators in inflammatory cells such as monocytes, macrophages, fibroblasts and endothelial cells. It is of note that the activity of the NF-κB system can be inhibited by several drugs such as corticosteroids, leflunomide, cyclosporin A, tacrolimus, high concentrations of sulphasalazine and aspirin, and concentrations of oxaprozin achievable in vivo. Consequently, the possibility of controlling the NF-κB system pharmacologically raises opportunities for developing approaches to interfere with the transformation of transient to persistent inflammatory responses.

Nuclear factor signal transduction T-lymphocytes anti-inflammatory drugs oxaprozin. 

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Copyright information

© VSP 2002 2002

Authors and Affiliations

  • Franco Dallegri
  • Luciano Ottonello

There are no affiliations available

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