Acute stimulation of the hypothalamic-pituitary-adrenal axis by IL-1 beta, TNF alpha and IL-6: a dose response study.
We investigated the effects of i.v. and intracerebroventricular (i.c.v) administration of increasing doses of recombinant human IL-1 beta, TNF alpha and IL-6 on plasma corticosterone (B) levels in rats. Rats were equipped with a jugular cannula for repeated blood sampling anda subgroup of rats also received an i.c.v implanted cannula. I.v. administration of IL-1 beta, TNF alpha or IL-6 and i.c.v administration of IL-1 beta and IL-6 induced a significant dose-dependent increase in plasma B levels, whereas i.c.v injection of TNF alpha in doses up to 1000 ng/rat was not effective. I.v. pretreatment of rats with anti-CRH antiserum had no significant overall effect on the plasma B response to i.v. administered IL-1 beta (500 and 3000 ng/rat), whereas the plasma B response to i.v. TNF alpha or IL-6 administration (3000 ng/rat) were significantly reduced. I.v. pretreatment of the animals with recombinant human IL-1 receptor 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 increases in plasma B levels were not affected. Our data show that 1) i.v. administration of IL-beta, TNF alpha or IL-6 and i.c.v administration of IL-1 beta or IL-6 dose-dependently stimulate the HPA axis; 2) when given i.v. or i.c.v, IL-1 beta is more powerful than TNF alpha and IL-6 in activating the HPA axis; 3) endogenous CRH is involved in the activation of the HPA axis by acute i.v. administration of TNF alpha and IL-6. It is most likely that in case of i.v. treatment with IL-1 beta a CRH-independent mechanism is involved. This study provides no arguments for the involvement of endogenous IL-1 in TNF alpha- or IL-6-induced activation of the HPA axis.
van der Meer
M J
MJ
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Sweep
C G
CG
Rijnkels
C E
CE
Pesman
G J
GJ
Tilders
F J
FJ
Kloppenborg
P W
PW
Hermus
A R
AR
D000311:Adrenal Glands / Q000502:physiology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000276:immunology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007031:Hypothalamus / Q000502:physiology*; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000494:pharmacology; D015850:Interleukin-6 / Q000008:administration & dosage* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010902:Pituitary Gland / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000494:pharmacology
D000906:Antibodies; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone