title: Endogenous expression of interleukin-4 regulates macrophage activation and confines cavity formation after traumatic spinal cord injury.
abstract: Traumatic spinal cord injury (SCI) triggers inflammatory reactions in which various types of cells and cytokines are involved. Several proinflammatory cytokines are up-regulated after SCI and play crucial roles in determining the extent of secondary tissue damage. However, relatively little is known about antiinflammatory cytokines and their roles in spinal cord trauma. Recent studies have shown that an antiinflammatory cytokine, interleukin-4 (IL-4), is expressed and exerts various modulatory effects in CNS inflammation. We found in the present study that IL-4 was highly expressed at 24 hr after contusive SCI in rats and declined thereafter, with concurrent up-regulation of IL-4 receptor subunit IL-4alpha. The majority of IL-4-producing cells were myeloperoxidase-positive neutrophils. Injection of neutralizing antibody against IL-4 into the contused spinal cord did not significantly affect the expression levels of proinflammatory cytokines such as IL-1beta, IL-6, and tumor necrosis factor-alpha or other antiinflammatory cytokines such as IL-10 and transforming growth factor-beta. Instead, attenuation of IL-4 activity led to a marked increase in the extent of ED1-positive macrophage activation along the rostrocaudal extent at 7 days after injury. The enhanced macrophage activation was preceded by an increase in the level of monocyte chemoattractant protein-1 (MCP-1/CCL2). Finally, IL-4 neutralization resulted in more extensive cavitation at 4 weeks after injury. These results suggest that endogenous expression of antiinflammatory cytokine IL-4 regulates the extent of acute macrophage activation and confines the ensuing secondary cavity formation after spinal cord trauma.
authors.affiliation: Brain Disease Research Center, Institute for Medical Sciences, and Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Seung Ihm
authors.initials: SI
authors.lastname: Lee
authors.forename: Soo Ryeong
authors.initials: SR
authors.lastname: Jeong
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kang
authors.forename: Dae Hee
authors.initials: DH
authors.lastname: Han
authors.forename: Byung Kwan
authors.initials: BK
authors.lastname: Jin
authors.forename: Uk
authors.initials: U
authors.lastname: Namgung
authors.forename: Byung G
authors.initials: BG
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000096:biosynthesis; D003288:Contusions / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000096:biosynthesis*; D008262:Macrophage Activation / Q000502:physiology*; D009410:Nerve Degeneration / Q000473:pathology; D020556:Neutrophil Infiltration; D051381:Rats; D017207:Rats, Sprague-Dawley; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D017931:DNA Primers; D019948:Receptors, Interleukin-4; D016212:Transforming Growth Factor beta; D015847:Interleukin-4