Serum levels of β2-microglobulin, neopterin, TNF-α and soluble receptors of TNF-α and interleukin-2 in intravenous drug abusers according to HIV-1 status and stage of the HIV-1 infection

Abstract

OBJECTIVE: To compare the serum levels of beta2-microglobulin (beta2M), neopterin (NP), TNF-alpha and soluble receptors of TNF-alpha (sTNF-R55 and sTNF-R75) and interleukin-2 (sIL-2R) in a population of intravenous drug abusers according to whether or not they had HIV-1 infection and to the stage of the HIV-1 infection. METHODS: A cross-sectional study was performed at four drug detoxification centers in Barcelona, and the HIV outpatient clinic at Hospital Clínic in Barcelona. Three cohorts of intravenous drug abusers (IVDAs)-105 HIV-1-uninfected patients (cohort A), 174 with asymptomatic HIV-1 infection (cohort B) and 39 with AIDS (cohort C)-were enrolled. On the first visit, the following laboratory tests were performed: hemogram and platelet count, hepatitis B surface antigen (HBsAg), anti-hepatitis C antibodies, B2M, NP, sIL-2R, TNF-alpha, and TNF receptors (sTNF-R55 and sTNF-R75). RESULTS: The three cohorts were homogeneous according to sex, type of drug, average number of intravenous doses of drug in 1 day, and hepatitis B infection. Patients with AIDS were older than those of cohort A and B (p<0.0001). HIV-negative IVDAs were co-infected with hepatitis C virus less frequently than were HIV-positive IVDAs (80% versus 91%, p<0.03). Among HIV-1-negative IVDAs (cohort A), almost all (from 86% to 95%, depending on the marker) individual values were within the normal boundaries of our laboratory. With a single exception (level of sTNF-R55 in cohort B compared with cohort A, p=0.15), levels of all markers were significantly higher in asymptomatic HIV-1-infected (cohort B) when compared with uninfected patients (cohort A), and in AIDS patients (cohort C) when compared with both cohorts A and B. There was a significant positive correlation between levels of ss2M and NP (r=0.56; p<0.01), ss2M and TNF (r=0.65, p<0.01) and NP and TNF (r=0.76, p<0.01). There was no correlation between levels of sIL-2R and levels of ss2M, NP or TNF and its receptors. CONCLUSIONS: Intravenous drug abuse does not modify serum levels of ss2M, NP, sIL-2R, TNF-alpha, and TNF receptors (sTNF-R55 and sTNF-R75). Levels of these markers increase significantly when an HIV-1 infection occurs and when there is progression to AIDS.

Diminished Production of Monocyte Proinflammatory Cytokines during Human Immunodeficiency Virus Viremia Is Mediated by Type I Interferons

“…Increases in serum levels of these cytokines have only intermittently been observed in the earliest stages of HIV infection, similar to the case for patients in the present study compared to uninfected controls. However, increases have been better documented for patients with advanced disease (3,4,18,54). These data are, in general, consistent with those of the present study.…”

Is HIV infection a TNF receptor signalling-driven disease?

“…In the early stages of infection, HIV proteins mimic TNFR signalling and favour sustained viral growth In the early stages of HIV infection, and in the context of low levels of plasma TNF [5,7,8], virally encoded proteins, particularly Nef, Vpr, and Tat, mimic TNFR signalling, resulting in sustained viral growth within infected cells, especially macrophages ( Figure 1). …”