TY - JOUR
T1 - Inflammatory mediators in diabetic and non-diabetic lumbosacral radiculoplexus neuropathy
AU - Kawamura, Nobutoshi
AU - Dyck, P. James B.
AU - Schmeichel, Ann M.
AU - Engelstad, Ja Nean K.
AU - Low, Phillip A.
AU - Dyck, Peter J.
N1 - Funding Information:
Supported in part by grants obtained from the National Institute of Neurological Disease and Stroke (NS 36797) (NS 32352) (NS 22352) (NS 43364).
PY - 2008/2
Y1 - 2008/2
N2 - 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-α (TNF-α), interleukin-6 (IL-6), and nuclear factor αB (NF-αB). 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-α expression was seen in Schwann cells and some macrophages of DLRPN and LRPN nerves, whereas IL-6 expression was minimal. There was greater NF-αB immunoreactivity in vessels and endoneurial cells of DLRPN and LRPN nerves than of the controls (P < 0.001). NF-αB expression correlated with the number of empty nerve strands (P < 0.01) and the frequency of axonal degeneration (P < 0.05), whereas TNF-α 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.
AB - 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-α (TNF-α), interleukin-6 (IL-6), and nuclear factor αB (NF-αB). 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-α expression was seen in Schwann cells and some macrophages of DLRPN and LRPN nerves, whereas IL-6 expression was minimal. There was greater NF-αB immunoreactivity in vessels and endoneurial cells of DLRPN and LRPN nerves than of the controls (P < 0.001). NF-αB expression correlated with the number of empty nerve strands (P < 0.01) and the frequency of axonal degeneration (P < 0.05), whereas TNF-α 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.
KW - Diabetic amyotrophy
KW - Diabetic lumbosacral radiculoplexus neuropathy
KW - Intercellular adhesion molecule-1
KW - Nuclear factor kappa B
KW - Peripheral neuropathy
KW - Tumor necrosis factor
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U2 - 10.1007/s00401-007-0326-2
DO - 10.1007/s00401-007-0326-2
M3 - Article
C2 - 18064475
AN - SCOPUS:38349018274
SN - 0001-6322
VL - 115
SP - 231
EP - 239
JO - Acta neuropathologica
JF - Acta neuropathologica
IS - 2
ER -