Sequential expression of mRNA for proinflammatory cytokines and interleukin-10 in the rat peripheral nervous system: comparison between immune-mediated demyelination and Wallerian degeneration.
This study examined the time course of mRNA levels of the proinflammatory cytokines interferon-gamma (IFNgamma), interleukin-1beta (IL1beta), interleukin-12 (IL12; p40 subunit), and the immunosuppressant interleukin-10 (IL10) by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) in rats with actively induced experimental autoimmune neuritis (EAN) and in distal stumps of crushed sciatic nerves undergoing Wallerian degeneration. In EAN IFNgamma- and IL1beta-mRNA peaked at the onset and acute phase of clinical disease. IL12p40-mRNA was upregulated later than IFNgamma-mRNA in the late acute phase from days 15 to 21. IL10-mRNA appeared concomitantly with the proinflammatory cytokines at day 11, but persisted at high levels into the clinical recovery phase. After nerve crush both IL1beta- and IL10-mRNA were rapidly upregulated in the distal stump at day 1 and slowly declined over the next 2 weeks. Significant levels of mRNA for IFNgamma could be found at days 4 and 7, whereas IL12p40-mRNA showed a biphasic induction. We provide evidence for a concomitant induction of pro- and anti-inflammatory cytokines in EAN. Moreover, the rapid upregulation in Wallerian degeneration suggests a more general role of cytokines in the biology of the peripheral nerve.