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Central Nervous Cytokine Patterns in Different Stages of HIV Infection
Thorsten Nolting*1, E Koutsilieri2, I W Husstedt3, N Gregor3, M Maschke4, M Obermann4, P Riederer2, S Sopper5, V ter Meulen2, G Arendt1, and Competence Network HIV/AIDS
1Univ Hosp of Duesseldorf, Germany; 2Univ of Wuerzburg, Germany; 3Univ Hosp of Muenster, Germany; 4Univ Hosp of Duisburg-Essen, Germany; and 5German Primate Ctr, Goettingen
Background: It is well known that cytokine patterns in the
central nervous system (CNS) of HIV-infected individuals differ from those of the
uninfected population. But it is unknown whether a rather inflammatory or anti-inflammtory, pro-apoptotic or anti-apoptotic cytokine
environment is present in different stages of the HIV-infection. The same is
true for the influence of HAART on cytokine patterns.
Methods: We included in the present study, 33 HIV+,
neurologically asymptomatic individuals, divided into non-AIDS and AIDS
patients and subdivided according to whether they were on HAART. Their data
were compared with those of 5 HIV– healthy controls. Cytokine levels
in cerebrospinal fluid (CSF) were detected with an antibody array.
Results: In non-AIDS patients without HAART, there is a
significant up-regulation of the inflammatory cytokines: interleukin (IL) -6, IL-12,
IL-18, monocyte chemoattractant protein 1 (MCP-1),
matrix metalloprotease
(MMP) -2, MMP-3, MMP-9, tumor
necrosis factor-alpha (TNF-α), and the apoptosis-inducing receptor TRAIL R1. The
anti-inflammatory cytokines, eg, IL-10, remain at
normal levels. This inflammation is in part reduced by HAART, but recurs in
treated AIDS patients, even when HAART is actually successful and there is no
history of drug failure. We find no clear correlation of cytokine patterns with
viral load, CSF routine parameters, and neuropsychological deficits in those
patients but a significant (eg, p = 0.009, TNF-α) correlation with duration of HIV-positivity.
Conclusions: HIV-1 provokes a long-lasting inflammatory
reaction in the CSF. This inflammation can be reduced by HAART in non-AIDS
patients. In ongoing disease, the inflammatory CSF reaction in AIDS patients
relapses independently from HAART. This may be one explanation for the absence
of positive influence of HAART on neuropsychological impairment that is
globally detected in the majority of neuroAIDS
cohorts. Additionally, anti-inflammatory therapeutic interventions combined
with an early start of HAART may be beneficial in HIV patients.
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