Interruptions of the HPA axis at any level
and through multiple mechanisms, whether on a genetic
basis, through surgical means such as adrenalectomy or
hypophysectomy, or with pharmacological interventions
such as treatment with the glucocorticoid receptor antag-
onist RU 486, can render an inflammatory resistant host
susceptible to inflammatory disease (Sternberg 1997a,b).
Imbalances of sympathetic nervous system responses are
also associated with autoimmune inflammatory diseases
such as arthritis in both humans and rodents. Human
juvenile rheumatoid arthritis has been associated with both
abnormal HPA axis and sympathoneuronal responses (Kuis
et al. 1996). Inflammatory susceptible LEW/N rats show
not only blunted HPA axis responsiveness, but also
blunted sympathoneuronal activity in response to gluco-
privic stress (Goldstein et al. 1993). This raises the question
of whether in such susceptible hosts multiple factors may
account for overall susceptibility to autoimmune/ inflammatory disease.
While this review has focused on the HPA axis and
glucocorticoids and their role in susceptibility to inflam-
matory disease, estrogen is known to play an extremely
important role in immune modulation, and contributes to
the approximately two- to tenfold higher ratio of most
autoimmune diseases in females of all species (Wilder
& Sternberg 1990, Ahmed et al. 1999, Lahita 1999).
Ovariectomy has been shown to reduce, while replace-
ment of estrogen re-constitutes, this di
