The Severity of Spinal Cord Injury Determines the Inflammatory Gene Expression Pattern after Immunization with Neural-Derived Peptides

Abstract

Previous studies revealed that the intensity of spinal cord injury (SCI) plays a key role in the therapeutic effects induced by immunizing with neural-derived peptides (INDP), as severe injuries abolish the beneficial effects induced by INDP. In the present study, we analyzed the expression of some inflammation-related genes (IL6, IL12, IL-1β, IFNɣ, TNFα, IL-10, IL-4, and IGF-1) by quantitative PCR in rats subjected to SCI and INDP. We investigated the expression of these genes after a moderate or severe contusion. In addition, we evaluated the effect of INDP by utilizing two different peptides: A91 and Cop-1. After moderate injury, both A91 and Cop-1 elicited a pattern of genes characterized by a significant reduction of IL6, IL1β, and TNFα but an increase in IL10, IL4, and IGF-1 expression. There was no effect on IL-12 and INFɣ. In contrast, the opposite pattern was observed when rats were subjected to a severe spinal cord contusion. Immunization with either peptide caused a significant increase in the expression of IL-12, IL-1β, IFNɣ (pro-inflammatory genes), and IGF-1. There was no effect on IL-4 and IL-10 compared to controls. After a moderate SCI, INDP reduced pro-inflammatory gene expression and generated a microenvironment prone to neuroprotection. Nevertheless, severe injury elicits the expression of pro-inflammatory genes that could be aggravated by INDP. These findings correlate with our previous results demonstrating that severe injury inhibits the beneficial effects of protective autoimmunity.

Keywords: Gene expression; Neural-derived peptides; Spinal cord injury.