Sensory impairments and delayed regeneration of sensory axons in interleukin-6-deficient mice.
Interleukin-6 (IL-6) is a multifunctional cytokine mediating inflammatory or immune reactions. Here we investigated the possible role of IL-6 in the intact or lesioned peripheral nervous system using adult IL-6 gene knockout (IL-6(-/-)) mice. Various sensory functions were tested by applying electrophysiological, morphological, biochemical, and behavioral methods. There was a 60% reduction of the compound action potential of the sensory branch of IL-6(-/-) mice as compared with the motor branch in the intact sciatic nerve. Cross sections of L5 DRG of IL-6(-/-) mice showed a shift in the relative size distribution of the neurons. The temperature sensitivity of IL-6(-/-) mice was also significantly reduced. After crush lesion of the sciatic nerve, its functional recovery was delayed in IL-6(-/-) mice as analyzed from a behavioral footprint assay. Measurements of compound action potentials 20 d after crush lesion showed that there was a very low level of recovery of the sensory but not of the motor branch of IL-6(-/-) mice. Similar results of sensory impairments were obtained with mice showing slow Wallerian degeneration (Wlds) and a delayed lesion-induced recruitment of macrophages. However, in contrast to WldS mice, in IL-6(-/-) mice we observed the characteristic lesion-induced invasion of macrophages and the upregulation of low-affinity neurotrophin receptor p75 (p75LNTR) mRNA levels identical to those of IL-6(+/+) mice. Thus, the mechanisms leading to the common sensory deficiencies were different between IL-6(-/-) and WldS mice. Altogether, the results suggest that interleukin-6 is essential to modulate sensory functions in vivo.
Zhong
J
J
Lehrstuhl für Molekulare Neurobiochemie, Ruhr-Universität Bochum, 44780 Bochum Germany.
Dietzel
I D
ID
Wahle
P
P
Kopf
M
M
Heumann
R
R
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology*; D048429:Cell Size; D006358:Hot Temperature; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009416:Nerve Regeneration; D009475:Neurons, Afferent / Q000502:physiology* / Q000648:ultrastructure; D017933:Peripheral Nervous System / Q000293:injuries*; D012584:Sciatic Nerve / Q000293:injuries; D012677:Sensation / Q000502:physiology*; D013997:Time Factors
D015850:Interleukin-6