Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients

Jun Chen; Jiasheng Shao; Rentian Cai; Yinzhong Shen; Renfang Zhang; Li Liu; Tangkai Qi; Hongzhou Lu

doi:10.1371/journal.pone.0100446

Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients

PLoS One. 2014 Jul 1;9(7):e100446. doi: 10.1371/journal.pone.0100446. eCollection 2014.

Authors

Jun Chen¹, Jiasheng Shao¹, Rentian Cai¹, Yinzhong Shen¹, Renfang Zhang¹, Li Liu¹, Tangkai Qi¹, Hongzhou Lu²

Affiliations

¹ Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
² Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; Department of Infectious Diseases, HuaShan Hospital, Fudan University, Shanghai, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, China.

Abstract

Background: Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.

Methods: We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).

Results: Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity.

Conclusions: IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anti-Retroviral Agents / therapeutic use*
CD4 Lymphocyte Count
Female
HIV Infections / drug therapy*
HIV Infections / metabolism
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
Kynurenine / blood
Kynurenine / metabolism
Lipopolysaccharide Receptors / blood
Male
Tryptophan / blood
Tryptophan / metabolism

Substances

Anti-Retroviral Agents
Indoleamine-Pyrrole 2,3,-Dioxygenase
Lipopolysaccharide Receptors
Kynurenine
Tryptophan

Grants and funding

JC and HL received grant from National Natural Science Foundation of China (No. 81301420 and 81071353, http://www.nsfc.gov.cn/). HL also received funding from Program for the 12th Five-year Plan (grant No. 2012ZX10001003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.