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Preliminary studies of cytokine-induced functional effects on the visual pathways in the rabbit
C F Brosnan1, M S Litwak, C E Schroeder
1Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Insights
Cytokines like interferon-gamma and TNF rapidly disrupt central nervous system (CNS) function in rabbits, causing temporary visual pathway delays. Interleukin-1 beta causes a slower, prolonged effect, highlighting cytokine-induced vascular changes in CNS inflammation.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Cytokines are key mediators of inflammation.
- Central nervous system (CNS) inflammation can lead to significant neurological deficits.
- Understanding cytokine roles in CNS inflammation is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the role of specific cytokines in inducing pathophysiological changes in the CNS.
- To examine the effects of interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and interleukin-1 beta (IL-1) on CNS function.
- To utilize the rabbit eye model to study inflammatory mediator effects in vivo.
Main Methods:
- Epidural visual evoked potentials (VEP) were recorded in rabbits.
- Intraocular injections of human recombinant IFN-gamma, TNF, and IL-1 beta were administered.
- Control substances were injected for comparison.
- Pathologic examination of ocular tissues was performed.
Main Results:
- IFN-gamma and TNF rapidly increased VEP peak latency (>2 ms) within 3 hours, effects reversible within 24 hours.
- IL-1 beta induced a progressive delay in VEP latency, peaking at 24 hours and resolving over 48 hours.
- Pathology revealed cytokine-induced vascular changes consistent with inflammation.
Conclusions:
- Acute, reversible CNS functional effects of these cytokines are linked to vascular events.
- The rabbit eye model is sensitive for studying in vivo inflammatory mediator effects on the CNS.
- Cytokines play a significant role in the vascular and functional changes associated with CNS inflammation.
Abstract:
Epidural visual evoked potentials (VEP) were used to study the role of cytokines in the induction of pathophysiologic changes associated with inflammation in the central nervous system (CNS) of the rabbit. In normal rabbits, intraocular injection of human recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) increased the peak latency of the cortical VEP by more than 2 ms within 3 h of injection; equal volume injections of control substances had no effect. Alterations in conduction induced by IFN-gamma and TNF reversed within 24 h and could be reinduced by reinjection. Intraocular injection of recombinant human interleukin-1 beta (IL-1) induced a more progressive delay in conduction that peaked 24 h after intraocular challenge and reversed over the ensuing 48 h. Pathologic examination of the tissues indicated that the primary effect of these cytokines is on the vasculature and induces changes associated with inflammation. The results suggest that the acute reversible effects of cytokines on CNS function are associated with vascular events; further they support the sensitivity of the 'rabbit eye model' for studies on the pathophysiologic effect of inflammatory mediators on the CNS in vivo.
