ACTH, Cortisol and Prolactin in Active Rheumatoid Arthritis

Abstract Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. ACTH, PRL, cortisol, IL-1β and TNF-α circadian rhythms have been studied in active RA (aRA) to evaluate a possible relationship between the neuroendocrine system and immunological activity in rheumatoid patients. ACTH, PRL, cortisol, PRL/cortisol ratio and IL-1β and TNF-α levels were determined in aRA patients and in control subjects at 6.00, 10.00, 14.00, 18.00, 22.00 and 02.00 h. In aRA patients we observed lower ACTH and cortisol levels at 22.00 h and 2.00 h, respectively and higher PRL and PRL/cortisol ratio at 2.00 h when compared to controls. IL-1β and TNF-α reached their highest serum levels in aRA patients at 2.00 and 6.00 h. This study provides evidence that in aRA there could be a temporary and probably causal relationship between diurnal disease activity, hormonal disequilibrium and cytokine secretion. An imbalance in favour of proinflammatory hormones (PRL and cytokines) as opposed to levels of anti-inflammatory hormones could be responsible for the diurnal rhythm of activity disease observed in aRA patients.

[1]  G. Chrousos,et al.  The three-way interactions between the hypothalamic-pituitary-adrenal and gonadal axes and the immune system. , 1996, Bailliere's clinical rheumatology.

[2]  A. Iranmanesh,et al.  Intensive venous sampling paradigms disclose high frequency adrenocorticotropin release episodes in normal men. , 1990, The Journal of clinical endocrinology and metabolism.

[3]  G. Chrousos,et al.  The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. , 1995, The New England journal of medicine.

[4]  G. Tougas,et al.  Evidence for anti-inflammatory effect of normal circulating plasma cortisol. , 1986, Clinical and experimental rheumatology.

[5]  C. Clevenger,et al.  Interleukin-2 driven nuclear translocation of prolactin in cloned T-lymphocytes. , 1990, Endocrinology.

[6]  G. Chrousos,et al.  Pituitary-adrenal axis responsiveness to ovine corticotropin releasing hormone in patients with rheumatoid arthritis treated with low dose prednisone. , 1992, The Journal of rheumatology.

[7]  G. Kingsley,et al.  Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis. , 1992, Arthritis and rheumatism.

[8]  C. Sweep,et al.  Similar response of adrenocorticotrophic hormone, cortisol and prolactin to surgery in rheumatoid arthritis and osteoarthritis. , 1998, British journal of rheumatology.

[9]  I. Bérczi,et al.  Immunodeficiency in hypophysectomized rats. , 1978, Acta endocrinologica.

[10]  A. Grossman,et al.  Neuroendocrine immune responses to inflammation: the concept of the neuroendocrine immune loop. , 1996, Bailliere's clinical rheumatology.

[11]  A. Cesano,et al.  Modulatory effect of prolactin on the resting and mitogen-induced activity of T, B, and NK lymphocytes , 1992, Brain, Behavior, and Immunity.

[12]  L. Matrisian,et al.  Prolactin receptors on human T and B lymphocytes: antagonism of prolactin binding by cyclosporine. , 1985, Journal of immunology.

[13]  J. Symons,et al.  CORRELATION OF PLASMA INTERLEUKIN 1 LEVELS WITH DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS , 1988, The Lancet.

[14]  G. Chrousos,et al.  Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. , 1997, The Journal of clinical endocrinology and metabolism.

[15]  A. Silman,et al.  Are both genetic and reproductive associations with rheumatoid arthritis linked to prolactin? , 1996, The Lancet.

[16]  M. Dallman,et al.  Corticosterone acts on the brain to inhibit adrenalectomy-induced adrenocorticotropin secretion. , 1988, Endocrinology.

[17]  G. Kingsley,et al.  Excessive and dysregulated secretion of prolactin in rheumatoid arthritis: immunopathogenetic and therapeutic implications. , 1993, British journal of rheumatology.

[18]  H. Imura,et al.  Cytokines and endocrine function: an interaction between the immune and neuroendocrine systems , 1991, Clinical endocrinology.

[19]  K. Nelson,et al.  Are both genetic and reproductive associations with rheumatoid arthritis linked to prolactin , 1996 .

[20]  A. Lewy,et al.  Circadian rhythm abnormalities in totally blind people: incidence and clinical significance. , 1992, The Journal of clinical endocrinology and metabolism.

[21]  E. Morand,et al.  Abnormal hypothalamic-pituitary-adrenal axis function in rheumatoid arthritis. Effects of nonsteroidal antiinflammatory drugs and water immersion. , 1994, Arthritis and rheumatism.

[22]  I. Bérczi The Immunology of Prolactin , 1992 .

[23]  J. Abrams,et al.  Synergistic roles of interleukin-6, interleukin-1, and tumor necrosis factor in the adrenocorticotropin response to bacterial lipopolysaccharide in vivo. , 1993, Endocrinology.

[24]  I. Chikanza,et al.  Hypothalamic-pituitary mediated modulation of immune function: prolactin as a neuroimmune peptide. , 1991, British journal of rheumatology.

[25]  R. Geenen,et al.  Diurnal rhythm of salivary cortisol levels in patients with recent-onset rheumatoid arthritis. , 2000, Arthritis and rheumatism.

[26]  R. Wilder,et al.  Hormones and autoimmunity: animal models of arthritis. , 1996, Bailliere's clinical rheumatology.

[27]  E. Sternberg Neuroendocrine factors in susceptibility to inflammatory disease: focus on the hypothalamic-pituitary-adrenal axis. , 1995, Hormone research.

[28]  B. Skogseid,et al.  Intact adrenocorticotropic hormone secretion but impaired cortisol response in patients with active rheumatoid arthritis. Effect of glucocorticoids. , 1996, The Journal of rheumatology.

[29]  W. Pierpaoli,et al.  Interdependence of thymic and neuroendocrine functions in ontogeny. , 1976, Clinical and experimental immunology.

[30]  E. Hooghe-Peters,et al.  Growth hormone and prolactin are paracrine growth and differentiation factors in the haemopoietic system. , 1993, Immunology today.

[31]  L. Matrisian,et al.  Prolactin receptors on human lymphocytes and their modulation by cyclosporine. , 1984, Biochemical and biophysical research communications.

[32]  H. Schatz,et al.  [Rheumatoid arthritis. Interactions between the endocrine and immune systems]. , 2009, Deutsche Medizinische Wochenschrift.

[33]  I. Bérczi,et al.  The immune effects of neuropeptides. , 1996, Bailliere's clinical rheumatology.

[34]  C. Clevenger,et al.  Requirement of nuclear prolactin for interleukin-2--stimulated proliferation of T lymphocytes. , 1991, Science.

[35]  K. Kovacs,et al.  Regulation of humoral immunity in rats by pituitary hormones. , 1981, Acta endocrinologica.

[36]  I. Bérczi,et al.  Prolactin deficiency in rheumatoid arthritis. , 1991, The Journal of rheumatology.