Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

It is clear that systemic administration of TNF-a not only elicits behavioral and neuroendocrine consequences, but also has pronounced central neurochemical effects. It remain to be established whether these are a direct effect of the cytokine treatment or secondary to the malaise engendered by the a TNF-a. Whatever the case it appeared that the neuroendocrine and central neurochemical effects of the cytokine were subject to a time-dependent sensitization. In particular, HPA activity, as reflected by levels of circulating corticosterone, may be enhanced when TNF-a reexposure occurs 14-28 days after initial treatment, but suppressed when reexposure occurs 24 h after initial administration. Of particular interest was the finding that the sensitization of noradrenergic utilization within the PVN essentially paralled the corticoid and behavioral changes, whereas a distinct sensitization was evident after a much earlier time interval (24 h) in the PFC. These findings have potentially important implications for immunotherapy, just as the effects of IL-1 are pertinent in this respect. For instance, some of the psychiatric disturbances seen in patients receiving immunotherapy (e.g., after IL-2) may be related to alterations in CNS neurotransmitter activity, particularly when the therapeutic regimen involves repeated administration of the cytokine.

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