INVESTIGADORES
GIOVAMBATTISTA Andres
artículos
Título:
Decreased hypothalamo-pituitary-adrenal axis response to neuroendocrine challenge under repeated endotoxemia.
Autor/es:
HADID R; SPINEDI, E; GIOVAMBATTISTA A; CHAUTARD T; GAILLARD, R
Revista:
NEUROIMMUNOMODULATION.
Editorial:
KARGER
Referencias:
Lugar: Basel; Año: 1996 vol. 3 p. 62 - 68
ISSN:
1021-7401
Resumen:
It has been established that in vivo administration of bacterial
lipopolysaccharide (LPS) enhances hypothalamo-pituitary-adrenal (HPA) axis
function by a mechanism involving endotoxin-stimulated cytokine release. Since
under chronic LPS treatment a tolerance of the HPA axis response takes place,
the aim of the present study was to determine whether mice submitted to
repeated LPS administration could present an impairment in the HPA response to
insulin (INS) administration, a pure neuroendocrine challenge. For this
purpose, adult female BALB/c mice were injected with 200 microliters i.p. of
sterile saline solution (VEH) containing 25 micrograms of LPS in a single or
repeated (at 24-hour intervals, during 5 consecutive days) fashion. Animals
were then killed at either 45 min after INS (0.3 IU/mouse, i.p.) or 2 h after
LPS (25 micrograms/mouse) administration on experimental day 1 (D1; without any
previous LPS injection), 3 (D3; mice having received 2 previous LPS injections)
or 5 (D5; mice having received 4 previous LPS administrations). Control groups
were injected a similar volume of VEH alone on experimental day 1 (D1; without
any previous LPS injection), 3 (D3; mice having received 2 previous LPS
injections) or 5 (D5; mice having received 4 previous LPS administrations); in
each group, mice were killed at either 45 min or 2 h after VEH injection.
Immediately after decapitation, trunk blood was collected. Plasma tumor
necrosis factor alpha (TNF), ACTH and corticosterone (B) levels were determined
by specific assays. Plasma TNF, ACTH and B levels were significantly increased
2 h after the first LPS treatment (D1). Although no significant increase in
plasma TNF concentration was found 2 h after the third LPS injection (D3), the
corticotrope response was still significant and induced a full effect on
adrenal B output. Two hours after the fifth LPS administration (D5) TNF output
was minimal and the HPA axis response was significantly diminished. Finally,
the pattern of the HPA axis response to INS-induced hypoglycemia was similar to
that elicited after LPS challenge although somewhat delayed. Our results
indicate that: (1) TNF seems to play an important role in stimulating HPA axis
function after single but not after repeated endotoxin administration; and (2)
an impairment in the HPA axis response to both immuneneuroendocrine (LPS) and
neuroendocrine (INS) stimuli takes place after repeated LPS administration.
This study further suggests that the tolerance of the HPA axis response under
recurrent endotoxemia could be, at least partially, due to an impairment in both
immune (TNF output) and neuroendocrine functions.