Inflammation: "a natural experiment" for the systemic pathogenicity of cytokines.
It has previously been demonstrated that the overproduction of interleukin-6 (IL-6) is a key element in the clinical and biological abnormalities encountered in Castleman's disease (CD). The particular case of a male child with a localized form of CD is reported. In this patient, evidence was found of a correlation between systemic manifestations and circulating IL-6, and IL-6 gene overexpression in the germinal centers of hyperplastic lymph nodes. Circulating IL-6 levels were 10- to 100-fold higher than in all CD cases previously documented. This unique biological feature was closely associated with high levels of circulating IL-1 and tumor necrosis factor-alpha (TNF-alpha), which are known for their ability to induce and/or amplify IL-6 production. One month after surgical removal of the pathological lymph node, the clinical and biological abnormalities diminished, while circulating IL-6 levels dropped dramatically eight months later. It is worth noting that after resection, the time-course of the IL-6 decrease closely correlated with that of IL-1 and TNF-alpha. Considering that in various inflammatory diseases IL-1, TNF-alpha and IL-6 may act in a synergistic manner in inducing systemic manifestations, this case report raises new questions as to the nature of the systemic pathogenicity of cytokines in CD.
Herbelin
C
C
Unité Immuno-hématologie pédiatrique, Hôpital des Enfants-Malades, Université Paris V, France.
Roux-Lombard
P
P
Herbelin
A
A
Peuchmaur
M
M
De Groote
D
D
Griscelli
C
C
Dayer
J M
JM
Prieur
A M
AM
D005871:Castleman Disease / Q000097:blood* / Q000209:etiology / Q000601:surgery; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000601:surgery; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha