Interleukin-6 (IL6) and cellular response to facial nerve injury: effects on lymphocyte recruitment, early microglial activation and axonal outgrowth in IL6-deficient mice.
Nerve injury triggers numerous changes in the injured neurons and surrounding non-neuronal cells. Of particular interest are molecular signals that play a role in the overall orchestration of this multifaceted cellular response. Here we investigated the function of interleukin-6 (IL6), a multifunctional neurotrophin and cytokine rapidly expressed in the injured nervous system, using the facial axotomy model in IL6-deficient mice and wild-type controls. Transgenic deletion of IL6 caused a massive decrease in the recruitment of CD3-positive T-lymphocytes and early microglial activation during the first 4 days after injury in the axotomized facial nucleus. This was accompanied by a more moderate reduction in peripheral regeneration at day 4, lymphocyte recruitment (day 14) and enhanced perikaryal sprouting (day 14). Motoneuron cell death, phagocytosis by microglial cells and recruitment of granulocytes and macrophages into injured peripheral nerve were not affected. In summary, IL6 lead to a variety of effects on the cellular response to neural trauma. However, the particularly strong actions on lymphocytes and microglia suggest that this cytokine plays a central role in the initiation of immune surveillance in the injured central nervous system.
Galiano
M
M
Department of Neuromorphology, Max-Planck Institute for Neurobiology, Am Klopferspitz 18A, D-82152 Martinsried, Germany.
Liu
Z Q
ZQ
Kalla
R
R
Bohatschek
M
M
Koppius
A
A
Gschwendtner
A
A
Xu
S
S
Werner
A
A
Kloss
C U
CU
Jones
L L
LL
Bluethmann
H
H
Raivich
G
G
D000818:Animals; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005154:Facial Nerve / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D020220:Facial Nerve Injuries / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D005455:Fluorescent Antibody Technique; D005911:Gliosis / Q000276:immunology / Q000378:metabolism; D020439:Growth Cones / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D009046:Motor Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000235:genetics / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012183:Retrograde Degeneration / Q000235:genetics / Q000276:immunology; D013997:Time Factors
D015850:Interleukin-6; D009419:Nerve Tissue Proteins