Author(s): Chittiprol S, Kumar AM, Shetty KT, Kumar HR, Satishchandra P,
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Abstract BACKGROUND: It is well established that there is mutual interaction between the neuroendocrines and immune systems and that the disturbance in any one system could affect the function of the other. While there is a large body of evidence suggesting negative impact of human immunodeficiency virus type 1B (HIV-1B) infection on both immune and neuroendocrine systems, the consequence of HIV-1 clade C infection (with structural differences from HIV-1B virus) on these systems is not clearly understood. METHODS: We carried out a 2-year longitudinal study on plasma profile of adrenocorticosteroids, including cortisol and DHEAS and their relationship with declining CD4+ cell counts in neurologically asymptomatic HIV-C infected individuals (N=84) in order to understand the impact of HIV-1 clade C infection on adrenocortical dysfunction and its relationship with the progressive decline in the cell mediated immunity. RESULTS: We found that while plasma cortisol levels increased significantly at baseline in HIV-1C infected individuals compared to those in HIV-negative controls (HIV-1C+, 9.83+/-0.39 vs controls, 8.04+/-0.45; p<0.01), there was a significant decrease in DHEAS in HIV-1C+ individuals, compared to that in HIV-negative controls (81.02+/-4.9 vs 185.1+/-12.03, p<0.001), and consequently a significant increase in cortisol:DHEAS ratio in HIV-1 clade C infected persons (0.19+/-0.002 vs control 0.058+/-0.006; p<0.001). Moreover, in HIV-1C infected individuals, there was a strong positive correlation between DHEAS and CD4 cells (r=0.2; p<0.05), and a strong negative correlation between cortisol, as well as cortisol:DHEAS ratio and CD4 cells (r=-0.25; p<0.01; and r=-0.31; p<0.001, respectively). CONCLUSIONS: These findings suggest the persistent and progressive adrenocortical dysfunction during the asymptomatic phase of HIV infection, and that the evaluation of increase in plasma cortisol, a decrease in DHEAS, and an increase in cortisol:DHEAS ratio may serve as important biomarkers preceding the impending down regulation of CD4 cell counts and progressive decline in the immune system function in HIV-1C infection. Furthermore, these findings may indicate the dysregulation of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity, the enzyme involved in the biosynthesis of cortisol and DHEA through the pregnenolone-progesterone pathway, and that it may offer an opportunity for drug discovery targeting re-regulation of 3beta-HSD activity for potential therapeutic application in HIV-1C infection.
This article was published in Clin Chim Acta
and referenced in Journal of Clinical & Cellular Immunology