Cytokine and chemokine blockade as immunointervention strategy for the treatment of diffuse lung diseases

Cytokines and chemokines are essential components for the pathophysiology o f sarcoidosis. In the last decade, evidence has accumulated indicating that most of the events that lead to the alveolitis, granuloma formation and ti ssue injury are regulated by these mediators and their receptors. Recently, information on the possible pathogenetic role of cytokines has been transl ated into the development of potent cytokine antagonists which have proved to be powerful means of controlling disease activity in some inflammatory d iseases. Molecules capable of neutralizing tumor necrosis factor-alpha (TNF -alpha) are currently used in the clinical setting of rheumatoid arthritis and active Crohn's disease. TNF-alpha is one of most important cytokines in the pathogenesis of sarcoidosis: not unexpectedly, data suggest the real p ossibility of using anti-TNF strategies to treat refractory sarcoidosis. Th ese data are preliminary and should promote further clinical trials to conf irm both the efficacy and tolerability of anti-TNF agents when used in pati ents with sarcoidosis and other interstitial lung diseases which are charac terized by an up-regulation of TNF-alpha expression in the pulmonary milieu . Blockades of other inflammatory cytokines are also expected to be therape utic in sarcoidosis and other T-cell mediated diffuse lung diseases. In par ticular, therapies directed at neutralizing chemokines and other molecules which control trafficking and accumulation of immunocompetent cells are pot entially more selective and attractive but require a priori knowledge of pr ecise pathways regulating the inflammation state involving the alveolar and interstitial structures.