While all previous data convey the idea that IL-1 steers inflammation in the central nervous system of MPS patients, TNF-α seems otherwise involved in the periphery, mediating both pro-inflammatory and programmed cell death pathways: this cytokine existing as either a transmembrane or a soluble molecule may activate different signaling cascades and downstream genes, and is involved in the regulation of neurogenesis, myelination, blood-brain barrier permeability, and synaptic plasticity. The gene discussed is IL1B; the disease is mucopolysaccharidosis.