The role of cytokines in the pathogenesis of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is characterised by an accumulation of cells ('LCH cells') with the same phenotypic features as normal Langerhans cells found in skin and other organs. The pathogenesis of LCH is unknown but there is increasing evidence to implicate the involvement of lymphokines and proinflammatory cytokines in the tissue damage seen in this disorder. Apart from histiocytes, the lesions contain giant cells, macrophages, neutrophils, eosinophils, lymphocytes, plasma cells and occasional mast cells that are the hallmark of an inflammatory process. The role of cytokines in the recruitment of haemopoietic cells within inflammatory lesions has only recently been recognised. In this article, we review the possible role of cytokines in the pathogenesis of LCH, and provide an overview of the methods currently used to detect and quantitate them. An appreciation of the type, distribution and amount of different cytokines released within lesions can provide clues to the possible aetiology of LCH. Using immunoassays, in situ hybridisation and RT-PCR, increased amounts of IL-1, IL-3, IL-4, IL-8, GM-CSF, TNF alpha, TGF beta and LIF have been demonstrated in LCH lesions. Lymphocytes constitutively produce GM-CSF and IL-3 and, to a lesser degree, IL-1, IL-4 and LIF whilst histiocytes produce TNF alpha, IL-1 beta and GM-CSF.