Development and Treatments of Inflammatory Cells and Cytokines in Spinal Cord Ischemia-Reperfusion Injury

During aortic surgery, interruption of spinal cord blood flow might cause spinal cord ischemia-reperfusion injury (IRI). The incidence of spinal cord IRI after aortic surgery is up to 28%, and patients with spinal cord IRI might suffer from postoperative paraplegia or paraparesis. Spinal cord IRI includes two phases. The immediate spinal cord injury is related to acute ischemia. And the delayed spinal cord injury involves both ischemic cellular death and reperfusion injury. Inflammation is a subsequent event of spinal cord ischemia and possibly a major contributor to spinal cord IRI. However, the development of inflammatory mediators is incompletely demonstrated. And treatments available for inflammation in spinal cord IRI are insufficient. Improved understanding about spinal cord IRI and the development of inflammatory cells and cytokines in this process will provide novel therapeutic strategies for spinal cord IRI. Inflammatory cytokines (e.g., TNF-αand IL-1) may play an important role in spinal cord IRI. For treatment of several intractable autoimmune diseases (e.g., rheumatoid arthritis), where inflammatory cytokines are involved in disease progression, anti-inflammatory cytokine antagonist is now available. Hence, there is great potential of anti-inflammatory cytokine antagonist for therapeutic use of spinal cord IRI. We here review the mediators and several possibilities of treatment in spinal cord IRI.

Human Cytomegalovirus Immediate-Early 2 Protein IE86 Blocks Virus-Induced Chemokine Expression

ABSTRACT The effect of human cytomegalovirus (HCMV) gene expression on cytokine (beta interferon) and chemokine (RANTES, MIG, MCP-2, MIP-1α, and interleukin-8) expression was examined. We demonstrate that HCMV gene expression is required to suppress the transcriptional induction of these cytokines and that the HCMV immediate-early 2 gene product IE86 can effectively block the expression of cytokines and proinflammatory chemokines during HCMV and Sendai virus infection. Additionally, we present data on viral mutants and ectopic protein expression which demonstrate that pp65, another identified HCMV cytokine antagonist, is not involved in regulating these proinflammatory cytokines. This is the first report to demonstrate that IE86 can act to suppress virus-induced proinflammatory cytokine transcript expression, extending the antiviral properties of this multifunctional viral protein.