Interleukin-2 given to asymptomatic HIV-infected individuals leads to an exaggerated response of the pituitary gland to the action of CRH

• Published in: Clinical endocrinology (Oxford) Vol. 59; no. 1; pp. 104 - 109
• Main Authors: Witzke, Oliver, Winterhagen, Toni, Kribben, Andreas, Philipp, Thomas, Mann, Klaus, Reinhardt, Walter
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.2003; Blackwell
• Subjects: Adrenocorticotropic Hormone - blood; Adrenocorticotropic Hormone - metabolism; Adult; Analysis of Variance; Anti-HIV Agents - therapeutic use; Biological and medical sciences; Corticotropin-Releasing Hormone; Endocrinopathies; HIV Infections - blood; HIV Infections - drug therapy; Human viral diseases; Humans; Hydrocortisone - blood; Hydrocortisone - metabolism; Hypothalamus. Hypophysis. Epiphysis (diseases); Infectious diseases; Interleukin-2 - therapeutic use; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pituitary Gland - drug effects; Pituitary Gland - metabolism; Prospective Studies; Stimulation, Chemical; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Immunopathology; Endocrine gland; Cytokine; Corticotropin releasing factor; AIDS; Asymptomatic; Immune deficiency; Biological activity; Heavy metal; Infection; Interleukin 2; Viral disease; Pituitary gland
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1046/j.1365-2265.2003.01803.x

Summary background and aims Studies investigating the impact of interleukin‐2 (IL‐2) on the corticotroph axis have shown that IL‐2 can stimulate cortisol and ACTH secretion. However, the site, the time course and the mechanisms of IL‐2 stimulation of the corticotroph axis are still not known. The aim of this study was to gain insight into the mechanisms of IL‐2 stimulation of the corticotroph axis. patients and methods A total of 9 × 106 IU/day IL‐2 were given to 18 male HIV‐infected patients treated with a combination of HIV antiviral drugs (usually two reverse‐transcriptase inhibitors and one protease‐inhibitor) over a course of 4–5 days. Seven of these 18 patients received a second course of IL‐2. results Cortisol levels increased significantly (P < 0·001) from baseline levels (427 ± 118 nmol/l) to 746 ± 132 nmol/l after 4 days of IL‐2 therapy with a gradual decrease to baseline within 10 days after the end of therapy. ACTH showed a similar pattern rising from 5·9 ± 1·9 pmol/l at baseline to 12·4 ± 4·6 pmol/l on day 4 (P < 0·001). The cortisol response after CRH application (carried out at 15·00 h) was significantly more pronounced at the end of IL‐2 application (CRH test B, baseline: 330 ± 59 nmol/l, peak 774 ± 134 nmol/l, 135% increase) when compared to pretreatment (CRH test A, baseline: 226 ± 73 nmol/l, peak 459 ± 103 nmol/l, 103% increase, P ≤ 0·0001). The cortisol response 9 days after the end of IL‐2 administration showed a similar pattern when compared to pretreatment values. The ACTH response after CRH was essentially paralleled by the cortisol response (CRH test B, baseline: 6·1 ± 2·8 pmol/l, peak 16·0 ± 4·4 pmol/l, 170% increase; CRH test A, baseline: 4·3 ± 1·9 pmol/l, peak 9·2 ± 3·1 pmol/l, 110% increase, P = 0·0005). Furthermore, we observed higher ACTH and cortisol concentrations in the morning when compared to late afternoon values during treatment with IL‐2 [cortisol: baseline: 426 ± 73 nmol/l (8·00 h); 226 ± 73 nmol/l (15·00 h)]; day 4: [746 ± 132 nmol/l (8·00 h); 339 ± 59 nmol/l (15·00 h)]; ACTH: baseline: [5·9 ± 1·9 pmol/l (8·00 h); 4·3 ± 1·9 pmol/l (15·00 h)]; day 4: [12·4 ± 4·7 pmol/l (8·00 h); 6·1 ± 2·8 pmol/l (15·00 h)]. conclusion The data from this in vivo study suggest that IL‐2 most likely resulted in corticotroph hyperplasia leading to an exaggerated response of the pituitary gland to the action of CRH.