Pyrrole-imidazole polyamide-H promotes anti-inflammation during the acute phase of spinal cord injury

Spinal cord injuries (SCI) cause severe primary damage to the central nervous system during impact. Secondary damage continues to develop due to an imbalanced microenvironment. Interleukin-6 (IL-6) is responsible for recruiting other proinflammatory cytokines and acute phase proteins to the injury site. However, an excess of proinflammatory signaling can result in increased inflammation, axonal retraction, fibrosis, and extended wound healing. Pyrrole-imidazole polyamides (PIPs) are DNA sequence-selective small molecules capable of gene regulation. One of such molecules, PIP-H, displayed a 4 times greater downregulation for IL-6. The purpose of this study is to test the efficacy of PIP-H at reducing the pro-inflammatory cytokine and its subsequent effects on the microenvironment during the acute phase of injury. Adult C57BL/6 mice were subject to a moderate contusion SCI and treatment (saline, minocycline-hydrochloride, or PIP-H) immediately at the lesion site after injury. At 1 day post-injury, the animals were sacrificed for ELISA or immunohistochemistry analysis. Results show that PIP-H treatment significantly decreases the expression of IL-6, CD68, and GFAP as compared to saline and minocycline treatments. This study supports the use of PIP-H as an effective inhibitor of IL-6 gene expression. Downregulating the proinflammatory cytokine is believed to positively influence the microenvironment during the acute phase of injury.M.S.Includes bibliographical reference