The hypothalamic-pituitary-adrenal-immune axis. A critical assessment
M. P. Lilly and D. S. Gann
Department of Surgery, University of Maryland, Baltimore 21201.
The hypothalamic-pituitary-adrenal (HPA) system has been a model for
neuroendocrine control of responses of organisms to stressors since the
turn of the century. Despite this, the pathways by which infectious insults
interact with the HPA system remained poorly defined. Recently, evidence
has been presented suggesting that humoral mediators released by
inflammatory cells (cytokines) may participate in two-way communication
between the site of inflammation and the central nervous system. In this
review, we detail the current understanding of the responses of the HPA
system to the classic physiologic stimuli of hypovolemia and pain, with an
emphasis on the cellular mechanisms and mediators discovered in recent
years. We also examine the data substantiating a role of interleukin 1,
interleukin 6, and tumor necrosis factor in the direct humoral activation
of the HPA system and consider the evidence favoring a physiologic negative
feedback relationship between the HPA and the immune systems. Such as
interaction is an exciting concept with broad clinical implications.
However, we believe that the temporal and quantitative aspects of
experiments designed to evaluate this interaction must be carefully
evaluated to assure that true physiologic stimuli are studied and that the
responses observed are not due to pharmacologic effects of inflammatory
mediators acting through "classic" neuroendocrine pathways.
