Do cytokines play role in the pathogenesis of mucopolysaccharidosis
Asli Inci, Asburce Olgac, Canan Demirtas, Ilyas Okur, Gursel Biberoglu, Fatih Suheyl Ezgu, Leyla Tumer
The mucopolysaccharidoses (MPS) are a heterogeneous group of inborn errors of metabolism with an increased deposition of glycosaminoglycans in lysosomes (GAGs). In MPS, GAG leads to inflammatory pathway activation. In MPS models, studies have shown that accumulation of glycosaminoglycans in lysosomes causes activation of oxidative stress, and then apoptosis is triggered. In this study, the aim was to show whether GAG deposition could trigger the inflammatory processes via cytokines.
Forty-three MPS patients as patient group and 29 healthy children as control group were included in the study. Samples were taken before and after ERT from 8 MPS patients. 15 patients were treated with enzyme replacement and 28 patients could not be treated with the enzyme. Tumor necrosis alpha (TNF-Î±), interleukin 1-beta (IL-1Î²), interleukin 6 (IL-6) levels were studied by ELISA method. When cytokine levels of MPS patients and control groups were compared, cytokines were found to significantly increased (pâ‰¤0.05) in MPS patients. Pretreatment IL-6 and posttreatment IL-6 and IL-1Î² levels of patients treated with enzyme replacement therapy (ERT) were found near to control group. Pre-treatment and post-treatment TNF-Î± levels were found significantly higher in MPS patients than the control group that was significantly higher in the post-treatment group. In the MPS group of ERT treatment, IL-1Î² and TNF-Î± levels decreased significantly after ERT(pâ‰¤0.05). MPS patients had higher levels of IL-6 and TNF-Î± levels than the control group that revealed inflammatory pathway activation in MPS patients. The inflammatory process is prominent in MPS patients that GAG deposition leads to increase pro-inflammatory cytokines and oxidative stress. Although enzyme replacement therapy reduces glycosaminoglycan accumulation by preventing cytokine production, it might be more effective when given with antiinfllammatory mediators.
Key words: Aucopolysaccharidosis, inflammation, cytokines, tumor necrosis alpha, interleukin 1 beta, interleukin 6