Cortisol response to an acute injection of IL-2 in healthy subjects and cancer patients: a first immunoneuroendocrine standardized clinical test to explore the interactions between immune and neuroendocrine systems.

Preliminary clinical studies would suggest that the immune alterations characterizing severe human illnesses, such as autoimmune diseases and cancer itself, may depend at least in part on an anomalous psychoneuroendocrine regulation of the immunity. Unfortunately, at present the psychoneuroimmune interactions may be clinically investigated only by separately analyzing the neuroendocrine and the immune systems, since there is no standardized clinical test capable of detecting the physiological response of the endocrine secretion to an immune stimulation. One of the main endocrine functions influenced by the immune activation is the hypothalamic-pituitary-adrenal axis. In fact, several cytokines have appeared to stimulate cortisol secretion by acting at a central site. On this basis, a study was planned to evaluate cortisol response to an acute IL-2 injection in healthy subjects and metastatic cancer patients, in an attempt to standardize a clinical neuroendocrinoimmune test capable of documenting possible alterations of the link between neuroendocrine and immune systems. The study included 10 healthy subjects as a control group and 10 cancer patients with metastatic disease. Control subjects were evaluated in basal conditions to determine the physiological circadian rhythm of cortisol, and after the subcutaneous (SC) injection of IL-2 (3 and 9 million IU). IL-2 at 3 million IU stimulated cortisol release in all healthy controls and in none of the cancer patients. IL-2 at 9 million IU induced a significant increase in cortisol mean levels in cancer patients, whose values, however, were still significantly lower with respect to those seen in controls in response to IL-2 at 3 million IU. No important IL-2 related side-effect occurred. This study shows that an acute SC injection of low-dose IL-2 with a following evaluation of cortisol secretion may constitute a first standardized immunoendocrine test, capable of exploring the status of the physiological link between neuroendocrine and immune systems, and of documenting the existence of important alterations in human diseases related to an immune dysfunction, such as advanced cancer, which has appeared to be characterized by a hyposensitivity of the hypothalamic-pituitary-adrenal axis to an acute cytokine administration.