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

Cytokines and chemokines are essential components for the pathophysiology of sarcoidosis. In the last decade, evidence has accumulated indicating that most of the events that lead to the alveolitis, granuloma formation and tissue injury are regulated by these mediators and their receptors. Recently, information on the possible pathogenetic role of cytokines has been translated into the development of potent cytokine antagonists which have proved to be powerful means of controlling disease activity in some inflammatory diseases. 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 possibility of using anti-TNF strategies to treat refractory sarcoidosis. These data are preliminary and should promote further clinical trials to confirm both the efficacy and tolerability of anti-TNF agents when used in patients with sarcoidosis and other interstitial lung diseases which are characterized by an up-regulation of TNF-alpha expression in the pulmonary milieu. Blockades of other inflammatory cytokines are also expected to be therapeutic in sarcoidosis and other T-cell mediated diffuse lung diseases. In particular, therapies directed at neutralizing chemokines and other molecules which control trafficking and accumulation of immunocompetent cells are potentially more selective and attractive but require a priori knowledge of precise pathways regulating the inflammation state involving the alveolar and interstitial structures.