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

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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.
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Document Type: Research Article

Affiliations: 1: Department of Medicine, Clinic of Nephrology and Hypertension, University Clinic Essen, Germany 2: Department of Medicine, Clinic of Endocrinology and

Publication date: July 1, 2003

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