INTERLEUKIN-13 STIMULATES NEURITE OUTGROWTH IN VITRO IN PRIMARY NEURONS AND ORGANOTYPIC BRAIN SLICES WHILE IT WORSENS CLINICAL OUTCOME AFTER SPINAL CORD INJURY IN VIVO

Abstract

There is increasing evidence that inflammatory processes after spinal cord injury (SCI) may exert detrimental as well as beneficial effects. Previous studies indicate that T helper type 2 cells may influence axonal regeneration via the production of anti-inflammatory cytokines such as interleukin-4 (IL-4) and IL-13. Objectives: In the current study we have investigated (i) the effects of IL-13 on axonal outgrowth and neuronal cell survival in vitro, as well as (ii) the in vivo therapeutic potential of recombinant IL-13 administered locally in gelfoam beads above the lesion at selected time points after hemisection SCI in mice. Results: In cortical primary neuron cultures, IL-13 significantly increased the average axonal length. To get closer to the in vivo situation we also analyzed the effects of IL-13 treatment on entorhinal cortex (EC) explants embedded in a three-dimensional collagen matrix from two-day-old wild type mice. Similarly, IL-13 was foundto be a potent modulator of neurite outgrowth in a dose-dependent manner. Analyses using viability assays on primary neuron cultures indicated no change of metabolic activity, suggesting no neuroprotective or toxic effects to be responsible for the increase in neurite outgrowth. In the in vivo situation, a single administration of IL-13 immediately after SCI significantly worsened locomotor recovery as assessed by the open-field Basso Mouse Scale. Interestingly, IL-13 effects seem to be restricted to the acute inflammatory phase after SCI, because treatment with IL-13 at 4 days after SCI had no effect. Conclusion: Although IL-13 is a potent regenerative (neurite growth inducing) agent in vitro, it causes worsening of clinical outcome when given in the acute phase after SCI or has no effect when administered later in the disease course. Thus, IL-13 cannot be used to treat SCI under the conditions tested in this study.