Decreased serum lipocalin-2 levels in human immunodeficiency virus-infected patients: increase during highly active anti-retroviral therapy

• Published in: Clinical and experimental immunology Vol. 152; no. 1; pp. 57 - 63
• Main Authors: Landrø, L, Damås, J.K, Flo, T.H, Heggelund, L, Ueland, T, Tjønnfjord, G.E, Espevik, T, Aukrust, P, Frøland, S.S
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-04-2008; Blackwell Publishing Ltd; Blackwell; Blackwell Science Inc
• Subjects: Acute-Phase Proteins; Adult; Analytical, structural and metabolic biochemistry; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Biological and medical sciences; bone marrow; Bone Marrow Cells - metabolism; CD4 Lymphocyte Count; Cells, Cultured; Female; Fundamental and applied biological sciences. Psychology; HAART; HIV; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1 - isolation & purification; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Lipocalin-2; Lipocalins - blood; Male; Medical sciences; Middle Aged; neutrophils; Neutrophils - metabolism; Proto-Oncogene Proteins - blood; RNA, Viral - blood; Translational Studies; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Human; Immunopathology; Retroviridae; AIDS; Increase; Biochemistry; Immune deficiency; Lentivirus; Infection; Virus; Treatment; HIV; Viral disease; Bone marrow; Antiviral; Serum; Neutrophil; Human immunodeficiency virus; lipocalin-2; neutrophils; HAART
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2008.03592.x

Although neutrophil gelatinase-associated lipocalin (NGAL) may play a pivotal role in the innate immune response, there are currently no data on NGAL levels in human immunodeficiency virus (HIV)-infected patients. In this study we aimed to examine the regulation of NGAL in HIV infection. The regulation of NGAL in HIV infection was examined by different experimental approaches, including studies in peripheral blood and mononuclear cells (MNC) from bone marrow aspirates before and during highly active anti-retroviral therapy (HAART). We found that: before initiating HAART, HIV-infected patients (n = 37) had significantly decreased serum NGAL levels compared with healthy controls (n = 26); (ii) during HAART, there was a gradual and significant increase in NGAL concentrations reaching levels comparable to those in healthy controls after 12 months; (iii) this increase was seen primarily in virological responders to HAART (HIV RNA level <200 copies/ml after 24 months); (iv) phytohaemagglutinin-stimulated NGAL release in MNC cells from bone marrow aspirates was decreased in untreated HIV-infected patients compared with healthy controls, but increased after 26 weeks on HAART; and (v) there was a significant positive correlation between neutrophil counts and NGAL levels at all time-points during HAART. We have shown decreased NGAL levels in HIV-infected patients, potentially reflecting decreased number and function of neutrophils as well as impaired bone marrow myelopoiesis. These abnormalities were reversed by successful HAART. Our findings underscore further the involvement of neutrophils and innate immunity in HIV-related immunodeficiency.