Cytokines in sarcoidosis.
Although the cause of sarcoidosis is still unknown, the combination of the characteristic morphologic aspect and the immunohistologic pattern of the sarcoid granulomatous lesions suggest that they are the result of an antigen-driven process. In particular, sarcoid granuloma is considered to be the consequence of an exaggerated immunological response against an undefined antigen which has persisted at the sites of disease involvement. Taking advantage of the availability of pure recombinant cytokines and molecular probes for cytokines and their receptors, in the last few years it has been possible to keenly study the involvement of several cytokines in the pathologic changes associated with sarcoidosis. The purpose of this review is to summarize the interactions between cytokines and their receptors which define regulatory networks ultimately contributing to the sarcoid granuloma formation at sites of disease activity. After a concise overview of the main cytokines involved in the sarcoid inflammatory response, we will briefly discuss the biological effects of Th1 and Th2 cytokines in sarcoid lung and then concentrate on the importance of the local production of those molecules whose release has been recently shown within the lung of patients with sarcoidosis, such as interleukin-12, interleukin-15, and chemokines. Furthermore, we will focus the discussion on the cytokines which, pivotal to the activation of the host defenses, may contribute to lung damage and the consequent lung fibrosis. The final section of this article reviews the lung release of cytokines in the context of recent hypotheses claiming microbial pathogens as putative causative agents of sarcoidosis.
Agostini
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Department of Clinical and Experimental Medicine, Padua University School of Medicine, Italy.
Semenzato
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D016207:Cytokines / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000378:metabolism; D018121:Receptors, Cytokine / Q000276:immunology; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*
D016207:Cytokines; D018121:Receptors, Cytokine