Inflammatory mediators in diabetic and non-diabetic lumbosacral radiculoplexus neuropathy.
Nerve microvasculitis and ischemic injury appear to be the primary and important pathogenic alterations in lumbosacral radiculoplexus neuropathy of patients with (DLRPN) and without (LRPN) diabetes mellitus (DM). Here, we examine the involvement of inflammatory mediators in DLRPN and LRPN. Paraffin sections of sural nerves from 19 patients with DLRPN, 13 patients with LRPN, and 20 disease control patients were immunostained for intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nuclear factor kappaB (NF-kappaB). The findings were correlated with histopathology. The pathologic and immunohistochemical alterations of DLRPN and LRPN nerves were indistinguishable. The nerves of both types of LRPN had a significantly greater number of ICAM-1 positive vessels than did the controls (P < 0.01). TNF-alpha expression was seen in Schwann cells and some macrophages of DLRPN and LRPN nerves, whereas IL-6 expression was minimal. There was greater NF-kappaB immunoreactivity in vessels and endoneurial cells of DLRPN and LRPN nerves than of the controls (P < 0.001). NF-kappaB expression correlated with the number of empty nerve strands (P < 0.01) and the frequency of axonal degeneration (P < 0.05), whereas TNF-alpha expression correlated inversely with the number of empty nerve strands of teased fibers (P < 0.05). Our findings suggest that up-regulation of inflammatory mediators target different cells at different disease stages and that these mediators may be sequentially involved in an immune-mediated inflammatory process that is shared by both DLRPN and LRPN. Up-regulated inflammatory mediators may be immunotherapeutic targets in these two conditions.
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Nobutoshi
N
Kawamura
P James B
PJ
Dyck
Ann M
AM
Schmeichel
JaNean K
JK
Engelstad
Phillip A
PA
Low
Peter J
PJ
Dyck
D000368:Aged; D003920:Diabetes Mellitus; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008160:Lumbosacral Plexus / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis; D011128:Polyradiculopathy / Q000378:metabolism* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1