Mjm. Vandermeer et al., ACUTE STIMULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS BY IL-1-BETA, TNF-ALPHA AND IL-6 - A DOSE-RESPONSE STUDY, Journal of endocrinological investigation, 19(3), 1996, pp. 175-182
We investigated the effects of iv and intracerebroventricular (icv) ad
ministration of increasing doses of recombinant human IL-1 beta, TNF a
lpha and IL-6 on plasma corticosterone (B) levels in rats. Rats were e
quipped with a jugular cannula for repeated blood sampling and a subgr
oup of rats also received an icy implanted cannula. Iv administration
of IL-1 beta, TNF alpha or IL-6 and icy administration of IL-1 beta an
d IL-6 induced a significant dose-dependent increase in plasma B level
s, whereas icy injection of TNF alpha in doses up to 1000 ng/rat was n
ot effective. Iv pretreatment of rats with anti-CRH antiserum had no s
ignificant overall effect on the plasma B response to iv administered
IL-1 beta (500 and 3000 ng/rat), whereas the plasma B response to iv T
NF alpha or IL-6 administration (3000 ng/rat) were significantly reduc
ed. Iv pretreatment of the animals with recombinant human IL-1 recepto
r antagonist (IL-1ra) significantly blocked the plasma B response to i
v treatment with IL-1 beta, whereas the TNF alpha- and IL-6-induced in
creases in plasma B levels were not affected. Our data show that: 1) i
v administration of IL-1 beta, TNF alpha or IL-6 and icy administratio
n of IL-1 beta or IL-6 dose-dependently stimulate the HPA axis; 2) whe
n given iv or icy, IL-1 beta is more powerful than TNF alpha and IL-6
in activating the HPA axis; 3) endogenous CRH is involved in the activ
ation of the HPA axis by acute iv administration of TNF alpha and IL-6
. It is most likely that in case of iv treatment with IL-1 beta a CRH-
independent mechanism is involved. This study provides no arguments fo
r the involvement of endogenous IL-1 in TNF alpha- or IL-6-induced act
ivation of the HPA axis.