Sarcoidosis: immunopathogenetic concepts and their clinical application

Abstract

Our understanding of the immunopathogenesis of sarcoidosis has been advanced by studies of bronchoalveolar lavage cells. Activated macrophages and T-cells have been identified in different compartments of the sarcoid lung and the characteristics of the activation suggest that the cells become activated in the course of a normal immune response. The immune cells communicate via a cytokine network and the measuring of cytokine levels yields subgroups of sarcoidosis patients with different courses of the disease indicating different states of activation of the disease-mediating immune cells. The causative agent of sarcoidosis has not yet been identified; however, some of the described mechanisms can be clinically applied either to detect patients at risk of deterioration or to develop new therapeutic strategies. Using these approaches methotrexate, pentoxifylline and thalidomide have been identified as drugs which effectively suppress sarcoid inflammation and the serum level of soluble interleukin-2 receptors has been delineated to be a serum marker of sarcoid inflammation. Furthermore, analysing the pulmonary cytokine network in sarcoidosis will yield new staging parameters possibly supplying prognostic information and guiding therapeutic intervention.