Tumor necrosis factor-alpha and nitric oxide in vertically HIV-1-infected children: implications for pathogenesis

• Published in: European cytokine network (Montrouge) Vol. 12; no. 3; p. 437
• Main Authors: González-Nicolás, J, Resino, S, Jiménez, J L, Alvarez, S, Fresno, M, Muñoz-Fernández, M A
• Format: Journal Article
• Language: English
• Published: France 01.07.2001
• Subjects: Cells, Cultured; Child, Preschool; Cross-Sectional Studies; Dose-Response Relationship, Drug; Dose-Response Relationship, Immunologic; Female; HIV Infections - immunology; HIV Infections - transmission; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - immunology; HIV-1 - pathogenicity; Humans; Infectious Disease Transmission, Vertical; Male; Nitric Oxide - biosynthesis; Nitric Oxide - blood; Nitric Oxide - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; omega-N-Methylarginine - pharmacology; Tumor Necrosis Factor-alpha - metabolism; Viral Load; Virus Replication - drug effects; Virus Replication - immunology
• ISSN: 1148-5493

We performed a cross-sectional study to investigate the plasma TNF-alpha and nitric oxide (NO) production in 44 vertically HIV-1-infected children, and the relationship with immunological status and viral replication. As a control group, 36 healthy, uninfected children were studied. Plasma TNF-alpha and NO levels were determined by ELISA. Viral load was quantified using standard assays. Cell proliferation, apoptosis and viral replication were evaluated in vitro by incorporation of (3H)-thymidine, flow cytometry and p24 antigen, respectively. Higher plasma TNF-alpha and NO levels were observed in HIV-1-infected children compared with healthy controls. We found a very strong correlation between plasma TNF-alpha and NO levels in HIV-1-infected children (r = 0.98; p < 0.001). Moreover, HIV-1-infected children with higher viral load (> 4.7 log10) showed higher TNF-alpha and NO levels than those with viral load below this threshold. Interestingly, we detected inducible nitric oxide synthase (iNOS) mRNA in T-lymphocytes from HIV-1-infected children. To address their possible patho-physiological significance, we tested the in vitro effects of NO and TNF-alpha in HIV-1 replication. Addition of TNF-alpha and NO donors to mitogen-activated, HIV-1-infected PBMC cultures produced a significant increase in viral replication. Moreover, HIV-1 replication in mitogen-stimulated, PBMC cultures was partially inhibited by iNOS specific inhibitors, and a neutralising, anti-TNF-alpha monoclonal antibody. Our results indicate that TNF-alpha and NO correlated with high viral load in HIV-1-infected children and favoured HIV-1 in vitro replication. These data suggest a detrimental role of NO in HIV-1 infection, and that NOS inhibitors may have some therapeutic benefit in HIV-1-infection.