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

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 x 10(6) 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
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.