Sensory impairments and delayed regeneration of sensory axons in interleukin-6-deficient mice

Interleukin-6 (IL-6) is a multifunctional cytokine mediating inflammatory o r immune reactions. Here we investigated the possible role of IL-6 in the i ntact or lesioned peripheral nervous system using adult IL-6 gene knockout (IL-6(-/-)) mice. Various sensory functions were tested by applying electro physiological, morphological, biochemical, and behavioral methods. There wa s 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 ner ve. Cross sections of L5 DRG of IL-6(-/-) mice showed a shift in the relati ve 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 delaye d in IL-6(-/-) mice as analyzed from a behavioral footprint assay. Measurem ents of compound action potentials 20 d after crush lesion showed that ther e was a very low level of recovery of the sensory but not of the motor bran ch of IL-6(-/-) mice. Similar results of sensory impairments were obtained with mice showing slow Wallerian degeneration (Wld(s)) 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 ma crophages and the upregulation of low-affinity neurotrophin receptor p75 (p 75LNTR) mRNA levels identical to those of 11-6(+/+) mice. Thus, the mechani sms leading to the common sensory deficiencies were different between IL-6( -/-) and Wld(s) mice. Altogether, the results suggest that interleukin-6 is essential to modulate sensory functions in vivo.