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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Tumor necrosis factor, interleukin 11, and leukemia inhibitory factor produced by Langerhans cells in Langerhans cell histiocytosis.

OBJECTIVES:: The etiology and pathophysiology of Langerhans cell histiocytosis (LCH) remain elusive. The 3-year survival in pediatric multisystem LCH is still around 80%, and children with risk organ involvement (i.e., liver, spleen, hematopoietic system, or lungs) have a less favorable outcome. To further elucidate the pathogenesis of LCH in the search for a rationale cure, the authors investigated intracellular synthesis of tumor necrosis factor (TNF), interleukin (IL)-11, and leukemia inhibitory factor (LIF) from biopsied lesions. METHODS:: Lesional cells were obtained by fine-needle aspiration biopsy from nine children with LCH. The study was accomplished by the use of an immunofluorescence staining method that allowed cytokine-producing cells to be differentiated from cytokine-binding cells. RESULTS:: All patients had histiocytes expressing TNF. Seven patients had histiocytes expressing IL-11 and six patients had histiocytes expressing LIF. The two children with the highest proportion of histiocytes displaying TNF and the three with the highest proportion of histiocytes expressing IL-11 and LIF all had risk organ involvement. Two-color staining revealed that histiocytes expressing TNF, IL-11, and LIF co-expressed CD1a molecules. CONCLUSIONS:: These observations suggest that LCH represents a cytokine-driven condition partially mediated by TNF, IL-11, and LIF. These three cytokines are all osteoclastogenic, suggesting a pathogenetic pathway for the osteolytic lesions in LCH. Furthermore, thrombocytosis in LCH may be explained by IL-11 and LIF activity.[1]


  1. Tumor necrosis factor, interleukin 11, and leukemia inhibitory factor produced by Langerhans cells in Langerhans cell histiocytosis. Andersson By, U., Tani, E., Andersson, U., Henter, J.I. J. Pediatr. Hematol. Oncol. (2004) [Pubmed]
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