Dynamic Toll-like receptor expression predicts outcome of sclerotherapy for lymphatic malformations with OK-432 in children

J Surg Res. 2014 Mar;187(1):197-201. doi: 10.1016/j.jss.2013.09.037. Epub 2013 Oct 2.

Abstract

Background: Sclerotherapy with OK-432 is recommended as a first-line treatment for lymphatic malformations. However, 40% of patients show poor response, defined by involution to <50% of the original size. It has been suggested that the OK-432 effect is highly dependent on the Toll-like receptor (TLR) 4-dependent expression of TLR7 in antigen-presenting cells. We hypothesized that the ability for TLR expression in monocytes after treatment with the TLR4-ligand lipopolysaccharide (LPS) can be used to predict successful OK-432 treatment.

Methods: Blood was taken from children with low responder (LR, n = 6) and high responder (HR, n = 5) of previous OK-432 treatment. Monocytes were stimulated with LPS for 20 h. TLR expression was analyzed with fluorescence-activated cell sorting (mean fluorescence intensity). The level of significance was P ≤ 0.05.

Results: The mean age of patients in the HR group was 1.4 ± 0.9 y and in the LR group 2.8 ± 2.9 y (P = 0.31). The mean TLR4 upregulation after LPS stimulation in the HR group was significantly higher than in the LR group (factor 3.6 versus factor 1 compared with nonstimulated controls; P = 0.037). The mean TLR7 expression did not show significant differences between the groups.

Conclusions: Dynamic TLR4 expression represents most probably a predictive parameter for the treatment of lymphatic malformations with OK-432 and should be further investigated.

Keywords: Children; Lymphatic malformation; OK-432; Sclerotherapy; Toll-like receptor.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Child, Preschool
  • Drug Monitoring / methods*
  • Female
  • Flow Cytometry
  • Humans
  • Infant
  • Ligands
  • Lipopolysaccharides / pharmacology
  • Lymphatic Abnormalities / metabolism
  • Lymphatic Abnormalities / therapy*
  • Male
  • Monocytes / drug effects
  • Monocytes / physiology
  • Picibanil / therapeutic use*
  • Predictive Value of Tests
  • Sclerotherapy / methods*
  • Toll-Like Receptor 4 / metabolism*
  • Toll-Like Receptor 7 / metabolism*
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents
  • Ligands
  • Lipopolysaccharides
  • TLR4 protein, human
  • TLR7 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptor 7
  • Picibanil