PMID- 8964868
OWN - NLM
STAT- MEDLINE
DCOM- 19961211
LR  - 20041117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 81
IP  - 6
DP  - 1996 Jun
TI  - Acute glucocorticoid deficiency is associated with plasma elevations of 
      interleukin-6: does the latter participate in the symptomatology of the steroid 
      withdrawal syndrome and adrenal insufficiency?
PG  - 2303-6
AB  - The cytokines tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and 
      IL-6 are secreted at inflammatory sites in tandem and play a crucial role in the 
      inflammatory and wound-healing processes. All three cytokines are potent 
      activators of the hypothalamic-pituitary-adrenal axis, through which they 
      restrain inflammation, whereas IL-6 itself plays a role in the termination of 
      inflammation as well. To test the hypothesis that endogenous glucocorticoids 
      exert a negative tonic effect on the secretion of these cytokines, we studied 17 
      patients with Cushing's disease and 2 patients with primary adrenal Cushing's 
      syndrome before and after surgery. Plasma TNF alpha, IL-1 beta and IL-6 were 
      measured before surgery, while the patients were hypercortisolemic; on 
      postoperative day 4 or 5, when they were hypocortisolemic; and on postoperative 
      day 9 or 10, when they were receiving glucocorticoid replacement. During severe 
      hypocortisolism, on postoperative day 4 or 5, plasma IL-6 levels rose 
      significantly, compared to the preoperative values (P < 0.001). During the same 
      interval, TNF alpha and IL-1 beta also rose, albeit to a lesser extent. Over the 
      same interval, patients with severe hypocortisolism experienced temperature 
      elevation, fatigue, somnolence, flu-like symptoms, and anorexia, symptoms that 
      have been traditionally attributed to glucocorticoid deficiency; these were also 
      experienced by subjects that received recombinant human IL-6. There was no 
      postoperative increase in any of the cytokines studied in the patients who were 
      not hypocortisolemic after surgery and who also lacked the corresponding 
      symptomatology. Plasma IL-6 concentrations decreased significantly, albeit not to 
      normal levels, in the hypocortisolemic group of patients on postoperative day 9 
      or 10, when they were receiving glucocorticoid replacement. We conclude that the 
      peripheral levels of IL-6 and to a lesser extent, those of TNF alpha and IL-1 
      beta are tonically inhibited by basal levels of glucocorticoids. The increased 
      IL-6 production that occurs when cortisol levels fall might explain the 
      symptomatology of acute glucocorticoid deficiency.
FAU - Papanicolaou, D A
AU  - Papanicolaou DA
AD  - Developmental Endocrinology Branch, National Institute of Child Health and Human 
      Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Tsigos, C
AU  - Tsigos C
FAU - Oldfield, E H
AU  - Oldfield EH
FAU - Chrousos, G P
AU  - Chrousos GP
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Glucocorticoids)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Acute Disease
MH  - Adrenal Glands/surgery
MH  - Adrenal Insufficiency/physiopathology
MH  - Adult
MH  - Aged
MH  - Body Temperature
MH  - Female
MH  - Glucocorticoids/administration & dosage/*deficiency/*therapeutic use
MH  - Humans
MH  - Interleukin-1/blood
MH  - Interleukin-6/*blood
MH  - Male
MH  - Middle Aged
MH  - Substance Withdrawal Syndrome/physiopathology
MH  - Tumor Necrosis Factor-alpha/analysis
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
AID - 10.1210/jcem.81.6.8964868 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1996 Jun;81(6):2303-6. doi: 10.1210/jcem.81.6.8964868.