Treatment of neuroinflammation by soluble tumor necrosis factor receptor Type II fused to a thermally responsive carrier: Laboratory investigation

Object Biochemical irritation of the dorsal root ganglion (DRG) after intervertebral disc herniation contributes to radiculopathy through tumor necrosis factor–α (TNFα)–mediated inflammation. Soluble TNF receptor Type II (sTNFRII) sequesters this cytokine, providing clinical benefit. Previous work involving conjugation of sTNFRII with thermally responsive elastin-like polypeptide (ELP) yielded a chimeric protein (ELP–sTNFRII) with in vitro anti-TNFα bioactivity. Furthermore, temperature-triggered ELP aggregation into a “depot” prolongs protein residence time following perineural injection. In this study the authors evaluated the inflammatory phenotype of DRG explants after TNFα stimulation, and assessed the abilities of sTNFRII or ELP–sTNFRII to attenuate these neuro-inflammatory changes. Methods Rat lumbar DRGs (35 animals) were treated in 6 groups, as follows: control; TNFα (25 ng/ml); TNFα with low-(0.2 μg/ml) or high-dose (1 μg/ml) sTNFRII; and TNFα with low-(52.5 μg/ml) or high-dose (262.5 μg/ml) ELP...