A novel immune-to-CNS communication pathway: cells of the meninges surrounding the spinal cord CSF space produce proinflammatory cytokines in response to an inflammatory stimulus.
Pain is enhanced in response to elevations of proinflammatory cytokines in spinal cerebrospinal fluid (CSF), following either intrathecal injection of these cytokines or intrathecal immune challenge with HIV-1 gp120 that induces cytokine release. Spinal cord glia have been assumed to be the source of endogenous proinflammatory cytokines that enhance pain. However, assuming that spinal cord glia are the sole source of CSF cytokines may be an underestimate, as the cellular composition of the meninges surrounding the spinal cord CSF space includes several cell types known to produce proinflammatory cytokines. The present experiments provide the first investigation of the immunocompetent nature of the spinal cord meninges. Here, we explore whether rat meninges are responsive to intrathecal gp120. These studies demonstrate that: (a) intrathecal gp120 upregulates meningeal gene expression of proinflammatory signals, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin 6 (IL-6), and inducible nitric oxide synthase (iNOS), and (b) intrathecal gp120 induces meningeal release of TNF-alpha, IL-1beta, and IL-6. In addition, stimulation of isolated meninges in vitro with gp120 induced the release of TNF-alpha and IL-1beta, indicating that the resident cells of the meninges are able to respond without immune cell recruitment. Taken together, these data document that the meninges are responsive to immunogenic stimuli in the CSF and that the meninges may be a source of immune products detected in CSF. The ability of the meninges to release to proinflammatory signals suggests a potential role in the modulation of pain.
Wieseler-Frank
Julie
J
Department of Psychology, University of Colorado, Boulder, CO, USA. frankjw@colorado.edu
Jekich
Brian M
BM
Mahoney
John H
JH
Bland
Sondra T
ST
Maier
Steven F
SF
Watkins
Linda R
LR
D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000134:cerebrospinal fluid / Q000276:immunology; D007121:Immunocompetence / Q000276:immunology / Q000502:physiology*; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008578:Meninges / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000502:physiology*; D010146:Pain / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000276:immunology
D015699:HIV Envelope Protein gp120; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D012333:RNA, Messenger