Tumor necrosis factor, interleukin 11, and leukemia inhibitory factor produced by Langerhans cells in Langerhans cell histiocytosis.
OBJECTIVE
: 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.
Andersson By
Ulrika
U
Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
Tani
Edneia
E
Andersson
Ulf
U
Henter
Jan-Inge
JI
D044963:Biopsy, Fine-Needle; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000150:complications / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007223:Infant; D017370:Interleukin-11 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007801:Langerhans Cells / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor; D008297:Male; D008856:Microscopy, Fluorescence; D010014:Osteolysis / Q000209:etiology; D013922:Thrombocytosis / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D014409:Tumor Necrosis Factor-alpha