Skip to main content
Log in

Evidence for a positive correlation between serum cortisol levels and IL-1β production by peripheral mononuclear cells in anorexia nervosa

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

A hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in anorexia nervosa (AN), together with some immunological abnormalities, involving citokine — and particularly Tumor Necrosis-Factor-α (TNF-α) — production by polymorphonuclear cells. The ability of pro-inflammatory cytokines to activate the HPA axis is well known; however, there are no data demonstrating an interdependence between immunological and endocrine response in AN. To investigate the presence of a correlation between immune response and pituitary-adrenal function, plasma ACTH and serum cortisol concentrations were measured in 13 AN patients and in the same number of controls. TNF-α and interleukin (IL)-1β production by ex-vivo unstimulated and LPS-stimulated peripheral mononuclear cells was also assessed. Circulating cortisol concentrations were higher (p<0.01) in AN (156.7±45.1 μg/l, mean±SD) than in controls (105.9±25.7 μg/l). Unstimulated IL-1β release in supernatants of mononuclear cell cultures was slightly but not significantly higher in AN than in controls, while TNF-α release was similar in the two groups. A positive correlation was found between IL-1β concentrations in unstimulated culture supranatants and serum cortisol levels in AN (r=0.782, p=0.002), while in normal subjects there was a trend toward a negative correlation; a slight positive correlation, while not significant, between IL-1β and plasma ACTH, as well as between TNF-α and serum cortisol was also found in AN. These data suggest that the normal relationship between pro-inflammatory cytokines release, particularly IL-1β and cortisol secretion is deranged in AN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, ed. 4. APA, Washington, DC, 1995, pp. 539–550.

    Google Scholar 

  2. Hurd H.P., Palumbo P.G., Garib H. Hypotalamic-endocrine disfunction in anorexia nervosa. Mayo Clin. Proc. 1977, 52: 711–715.

    CAS  PubMed  Google Scholar 

  3. Miyai K., Yamamoto T., Azukizama M., Ishibashi K., Kumahara Y. Serum thyroid hormones and thyrotropin in anorexia nervosa. J. Clin. Endocrinol. Metab. 1975, 40: 334–338.

    Article  CAS  PubMed  Google Scholar 

  4. Baranowska B., Rozbicka G., Jeske W., Abdel-Fattah M.H. The role of endogenous opiates in the mechanism of inhibited Luteinizing Hormone (LH) secretion in women with anorexia nervosa: the effect of naloxone on LH, Follicle Stimulating Hormone (FSH), Prolactin, and β Endorphin secretion. J. Clin. Endocrinol. Metab. 1984, 59: 412–416.

    Article  CAS  PubMed  Google Scholar 

  5. Gold P.W., Gwirtsman H., Avgerinos P.C., Nieman L.K., Gallucci W.T., Kaye W., Jimerson D., Ebert M., Rittmaster R., Loriaux D.L. Abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa. N. Engl. J. Med. 1986, 314: 1335–1342.

    Article  CAS  PubMed  Google Scholar 

  6. Hotta M., Shibasaki T., Masuda A., Imaki T., Demura H., Ling N., Shizume K. The responses of plasma adrenocorticotropin and cortisol to corticotropin-releasing hormone (CRH) and cerebrospinal fluid immunoreactive CRH in anorexia nervosa patients. J. Clin. Endocrinol. Metab. 1986, 62: 319–324.

    Article  CAS  PubMed  Google Scholar 

  7. Brambilla F., Ferrari E., Brunetta M., Peirone A., Draisci A., Sacerdote P., Panerai A. Immunoendocrine aspects of anorexia nervosa. Psychiatry Res. 1996, 62: 97–104.

    Article  CAS  PubMed  Google Scholar 

  8. Kaye W.H., Gwirstman H.E., George D.T., Ebert M.H., Jimerson D.C., Tomai T.P., Chrousos G.P., Gold P.W. Elevated cerobrospinal fluid levels of immunoreactive corticotropin-releasing hormone in anorexia nervosa: relation to state of nutrition, adrenal function and intensity of depression. J. Clin. Endocrinol. Metab. 1987, 64: 203–208.

    Article  CAS  PubMed  Google Scholar 

  9. Cavagnini F., Invitti C., Passamonti M., Polli E. Response of ACTH and cortisol to corticotropin-releasing hormone in anorexia nervosa. N. Engl. J. Med. 1986, 314: 184–185.

    CAS  PubMed  Google Scholar 

  10. Licinio J., Wong M., Gold P.W. The hypothalamic-pituitary-adrenal axis in anorexia nervosa. Psychiatry Res. 1996, 62: 75–83.

    Article  CAS  PubMed  Google Scholar 

  11. Holden R.J., Pakula I.S. The role of Tumor Necrosis Factor-α in the pathogenesis of anorexia and bulimia nervosa, cancer cachexia and obesity. Med. Hypotheses 1996, 47: 423–438.

    Article  CAS  PubMed  Google Scholar 

  12. Imura H., Fukata J. Endocrine-paracrine interaction in communication between the immune and endocrine systems. Activation of the hypothalamic-pituitary axis in inflammation. Eur. J. Endocrinol. 1994, 130: 32–37.

    Article  CAS  PubMed  Google Scholar 

  13. Perlstein R.S., Whitnall M.H., Abrams J.S., Mougey E.H., Neta R. Synergistic roles of Interleukin-6, Interleukin-1, and Tumor Necrosis Factor in the adrenocorticotropin response to bacterial lipopolysaccharide in vivo. Endocrinology 1993, 132: 946–952.

    CAS  PubMed  Google Scholar 

  14. Chrousos G.P. The hypothalamic-pituitary-adrenal axis and immunemediated inflammation. N. Engl. J. Med. 1995, 332: 1351–1362.

    Article  CAS  PubMed  Google Scholar 

  15. Harbuz M.S., Lightman S.L. Stress and the hypothalamo-pituitary-adrenal axis: acute, chronic and immunological activation. J. Endocrinol. 1992, 134: 327–339.

    Article  CAS  PubMed  Google Scholar 

  16. Vaisman N. Tumor necrosis factor during starvation. Am. J. Med. 1989, 87: 115.

    Article  CAS  PubMed  Google Scholar 

  17. Bessler H., Karp L., Notti I., Apter A., Tyano S., Djaldetti M., Weizman R. Cytokine production in anorexia nervosa. Clin. Neuropharmacol. 1993, 16: 237–243.

    Article  CAS  PubMed  Google Scholar 

  18. Polack E., Nahanod V.E., Emeric-Sauval E., Bello M., Costas M., Finkielman S., Artz E. Low lymphocyte interferon-gamma production and variable proliferative response in anorexia nervosa patients. J. Clin. Immunol. 1993, 136: 445–451.

    Article  Google Scholar 

  19. Schattner A., Steinbock M., Tepper R., Schonfeld A., Vaisman N., Hahn T. Tumour necrosis factor production and cell-mediated immunity in anorexia nervosa. Clin. Exp. Immunol. 1990, 79: 62–66.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Cason J., Ainley C.C., Wolstencroft R.A., Norton K.R.W., Thompson R.P.H. Cell-mediated immunity in anorexia nervosa. Clin. Exp. Immunol. 1986, 64: 370–375.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Pomeroy C., Eckert E., Hu S., Eiken B., Mentink M., Crosby R.D., Chao C.C. Role of Interleukin-6 and Transforming Growth Factor-β in anorexia nervosa. Biol. Psychiatry 1994, 36: 836–839.

    Article  CAS  PubMed  Google Scholar 

  22. deBont E.S., Niemarkt A.E., Tamminga R.Y., Kimpen J.L., Kamps W.A., de Leij L.H. Lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells: intracellular localization of tumor necrosis factor alpha and interleukin-1-beta detected with a three-color immunofluorescence technique. Histochem. Cell. Biol. 1996, 106: 593–598

    Article  CAS  Google Scholar 

  23. Cannon J.G., Norad J.L., Poutsiaka D.D., Dinarello C.A. Measuring circulating cytokines. J. Appl. Physiol. 1993, 75: 1897–1902.

    CAS  PubMed  Google Scholar 

  24. Muller K., Zak M., Nielsen S., Pedersen F.K., de Nully P., Bendtzen K. In vitro cytokine production and phenotype expression by blood mononuclear cells from umbilical cords, children and adults. Pediatr. Allergy Immunol. 1996, 7: 117–124.

    Article  CAS  PubMed  Google Scholar 

  25. Kontula K., Andersson L.C., Huttunen M., Pelkonen R. Reduced level of cellular glucocorticoid receptors in patients with anorexia nervosa. Horm. Metab. Res. 1982, 14: 619–620.

    Article  CAS  PubMed  Google Scholar 

  26. Armanini D., Spinella P., Simoncini M., Basso A., Zovato S., Pozzan G.B., De Palo C.B., Bucciante G., Karbowiak I. Regulation of corticosteroid receptors in patients with anorexia nervosa and Cushing’s syndrome. J. Endocrinol. 1998, 158: 435–439.

    Article  CAS  PubMed  Google Scholar 

  27. Girardin E., Garosci-Cholet M., Dechand H., Lejeune H., Carrier E., Tournaire J., Pugeat M. Glucocorticoid receptors in lymphocytes in anorexia nervosa. Clin. Endocrinol. 1991, 35: 79–84.

    Article  CAS  Google Scholar 

  28. Invitti C., Radaelli G., Baldi G., Cavagnini F. Glucocorticoid receptors in Anorexia Nervosa and Cushing’s disease. Biol. Psychiatry 1999, 45: 1467–1471.

    Article  CAS  PubMed  Google Scholar 

  29. Besedovsky H.O., Del Rey A. Immune-neuro-endocrine interactions: facts and hypotheses. Endocr. Rev. 1996, 17: 64–102.

    Article  CAS  PubMed  Google Scholar 

  30. Gomez, F., Lahmame A., de Klot E.R., Armario A. Hypothalamic-pituitary-adrenal response to chronic stress in five inbred rat strains: differential responses are mainly located at the adrenocortical level. Neuroendocrinology 1996, 63: 327–337.

    Article  CAS  PubMed  Google Scholar 

  31. Adcock I.M., Brown C.R., Barnes P.J. Tumour Necrosis Factor-β causes retention of activated glucocorticoid receptor within the cytoplasm of A549 cells. Biochem. Biophys. Res. Commun. 1996, 225: 545–550.

    Article  CAS  PubMed  Google Scholar 

  32. Verheggen M.M., van Hal P.T.W., Adriaansen-Soeting P.W.C., Goense P.J.A., Hoogsteden H.C., Brinkmann A.O., Versnel M.A. Modulation of glucocorticoid receptor expression in human bronchial epithelial cell lines by IL-1β TNF-α and LPS. Eur. Respir. J. 1996, 9: 2036–2043.

    Article  CAS  PubMed  Google Scholar 

  33. Holden R.J., Pakula I.S. The role of Tumor Necrosis Factor-β in the pathogenesis of anorexia and bulimia nervosa, cancer cachexia and obesity. Med. Hypotheses 1996, 47: 423–438.

    Article  CAS  PubMed  Google Scholar 

  34. Tominaga T., Fukata J., Naito Y., Usui T., Murakami N., Fukushima M., Nakai Y., Hirai Y., Imura H. Prostaglandin-dependent in vitro stimulation of adrenocortical steroidogenesis by interleukins. Endocrinology 1991, 128: 526–531.

    Article  CAS  PubMed  Google Scholar 

  35. Roh M.S., Drazenovich K.A., Barbose J.J., Dinarello C.A., Cobb C.F. Direct stimulation of the adrenal cortex by interleukin 1. Surgery 1987, 102: 140–146.

    CAS  PubMed  Google Scholar 

  36. Whitcomb R.W., Linehan W.M., Wahl L.M., Knazek R.A. Monocytes stimulate cortisol production by cultured human adrenocortical cells. J. Clin. Endocrinol. Metab. 1988, 66: 33–38.

    Article  CAS  PubMed  Google Scholar 

  37. Schultzberg M., Andersson C., Unden A., Troye-Blomberg M., Svenson S.B., Bartfai T. Interleukin-1 in adrenal chromaffin cells. Neuroscience 1989, 30: 805–810.

    Article  CAS  PubMed  Google Scholar 

  38. Bornstein S.R., Ehrhart-Bornstein M., Scherbaum W.A., Pfeiffer E.F., Holst J.J. Efffects of splanchnic nerve stimulation on the adrenal cortex may be mediated by chromaffin cells in a paracrine manner. Endocrinology 1990, 127: 900–906.

    Article  CAS  PubMed  Google Scholar 

  39. Bornstein S.R., González-Hernández J.A., Ehrhart-Bornstein M., Alder G., Scherbaum W.A. Intimate contact of chromaffin and cortical cells within the human adrenal gland forms the cellular basis for important intraadrenal interactions. J. Clin. Endocrinol. Metab. 1994, 78: 225–232.

    CAS  PubMed  Google Scholar 

  40. Biglino A., Limone P., Forno B., Pollono A., Cariti G., Molinatti G.M., Gioannini P. Altered adrenocorticotropin and cortisol response to corticotropin-releasing hormone in HIV-1 infection. Eur. J. Endocrinol. 1995, 133: 173–179.

    Article  CAS  PubMed  Google Scholar 

  41. Hesse D.G., Tracey K.J., Fong Y., Manogue K.R., Palladino M.A. Jr., Cerami A., Shires G.T., Lowry S.F. Cytokine appearance in human endotoxemia and primate bacteriemia. Surg. Gynecol. Obstet. 1988, 166: 147–153.

    CAS  PubMed  Google Scholar 

  42. van Deventer S.J.H., Buller H.R., Ten Cate J.W., Aarden L.A., Hack C.E., Sturk A. Experimental and endotoxemia in humans: analysis of cytokine release and coagulation, fibrynolitic, and complement pathways. Blood 1990, 76: 2520–2526.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Limone, P., Biglino, A., Bottino, F. et al. Evidence for a positive correlation between serum cortisol levels and IL-1β production by peripheral mononuclear cells in anorexia nervosa. J Endocrinol Invest 23, 422–427 (2000). https://doi.org/10.1007/BF03343750

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03343750

Key-words

Navigation