Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

XIV International AIDS Conference

Abstracts WePeA5793-WePeA5797 25

Presenting author: Pere Domingo, Hospital St. Pau, Internal Medicine, Av.
St. Antoni Ma Claret, 167, 08025 Barcelona, Spain, Tel.: [phone], Fax:
[phone], E-mail: [email protected]
WePeA5793 Changes in cytokine levels in the genital tract of
women infected with human immunodeficiency
virus type-1 (HIV) during treatment with highly
active antiretroviral therapy (HAART)
M. Till1, I. Helenowski1, A.W. Rademaker', A.L. Landay2. 1Northwestern
University Medical School, 676 N Saint Clair St, Suite 200, Chicago, Illinois,
60611, United States; 2Rush-Presbyterian-St Lukes Medical Center, Rush
University, Chicago, Illinois, United States
Background: The immune system of the female genital tract can be important
in regulating HIV replication. HIV-infected women have higher levels of inflammatory cytokines in cervicovaginal lavage (CVL) fluid. It is not known if HAART
affects genital tract cytokine production. The objective of this study was to evaluate changes in cytokine levels in the female genital tract after initiating potent
dual-protease inhibitor HAART.
Methods: CVL specimens were collected from women enrolled in a phase II clinical trial assessing efficacy of BID vs TID nelfinavir+saquinavir with BID stavudine+lamivudine. CVL specimens from 22 women at baseline (BL) and after 6
months of HAART (M6) were analyzed for the following cytokines: interferony(INFy), tumor necrosis factor-o (TNFo), interleukin-6 (IL6), IL13, IL8, IL10, IL2,
IL4, and IL12 by enzyme-linked immunosorbent assays.
Results: By M6 the peripheral mean CD4 count rose 146cells/ml (p<.0001
Signed Rank) and 17/22 had VL <400copies/ml. Most (68-100%) had detectable
levels of INFy, IL6, IL1, IL8 and 1L12 in their CVL fluid at BL and M6. Levels of
IL6 and IL15 stayed constant. IL10 was undetectable at BL, but was present in
24% at M6. INFy levels fell significantly with increasing CD4 count (p=.009 Spearman Correlation). The percentage of patients with inflammation, HPV or dysplasia
on Pap smear did not change from BL to M6.
Conclusions: There were changes in local immunity based on cytokine levels after initiation of HAART A fall in INFy level was seen with robust immune reconstitution. If transient increases in genital HIV VL occur (which were observed in this
study), a lack of IFNy effector function for cellular immune response could support local viral rebound. In addition, inflammatory cytokines IL6 and ILl13 which
promote viral replication persist over time. This could impact sexual as well as
vertical transmission warranting further study
Presenting author: Michele Till, 676 N Saint Clair St, Suite 200, Chicago, Illinois,
60611, United States, Tel.: [phone], Fax: [phone], E-mail: m-till
@ northwestern.edu
WePeA5794 Acylation stimulating protein (ASP) and tumor
necrosis factor (TNF) production in subcutaneous
adipose tissue of HIV-infected patients with and
without lipodystrophy
G. lonescu, Q. He, E.S. Engelson, J.A. Johnson, J.B. Albu, Y. Inada, D.P. Kotler.
St.Luke's-Roosevelt Hospital Center, 514 Fairview Avenue, Apt # 2R,
Ridgewood, NY 11385, United States
Background: Etiology of HIV-related lipodystrophy is multifactorial. Changes in
adipose tissue compartments may be related to altered adipocyte turnover or fat
storage. Promoters of adipose tissue growth and fat storage belong to the alternate pathway of complement. Factors D, B, C3 and its split product C3adesArg
(ASP) stimulate free fatty acid uptake into adipocytes and triglycerides synthesis.
Inflammatory cytokines, such as TNF, may promote local lipoatrophy.
Our aim was to see if fat redistribution is associated with alterations in the balance
of the paracrine factors, ASP and TNFo.
Methods: Aspirations of subcutaneous fat were performed in 22 subjects (5 HIV-, 8 HIV+ without lipodystrophy, HIVL-) and 9 HIV with lipodystrophy (HIVL+)
matched by age and BMI. Adipose tissue explants were incubated for 3 hours
to determine TNF release and for 3 days to measure ASP. TNF release, serum
levels of sTNF RII and ASP were quantitated by ELISA, C3 and C4 by immune adherence hemagglutination; factors B,D by hemolytic assay. C3 conversion to ASP
was calculated. Body fat compartments were quantitated by whole body MRI. We
used ANOVA and regression analysis for statistical comparison.
Results: Short term TNF release into the medium and serum concentration of
sTNF RII, were higher in HIVL+ than in HIVL- or controls (p=0.3). C3 production
was similar in all groups; absolute ASP production and % conversion of C3 to
ASP were lower in HIVL+ (p=0.05 and p<0.01, respectively). C3 conversion rate
to ASP was inversely associated with levels of sTNF RII (p= 0.043, R2=0.2). No
C4 was found.
Conclusions:1.Fat redistribution may be due to alterations in paracrine factors
that regulate adipose tissue mass.
2.Lipoatrophy may be the result of a relative deficiency of ASP production.
3.The observed deficiency in C3 conversion to ASP might be related to excess

local secretion of TNF, reflected by increased systemic levels of sTNF RII.
Presenting author: Gabriel Ionescu, 514 Fairview Avenue, Apt # 2R, Ridgewood, NY 11385, United States, Tel.: [phone], Fax: [phone], E-mail: [email protected]

WePeA5795 Cytokines in HIV-associated pulmonary
hypertension
A.M. Pellicelli, P. Noto, G. Liuzzi, P. De Longis, G. D'Offizi, N. Petrosillo. National
Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
Background: The direct role of HIV in the pathogenesis of HIV-associated pulmonary hypertension (HAPP) is still questionable, wheras an indirect role, mediated by circulating cytokines, cannot be excluded. Aim of the study was to assess
the role of circulating cytokines in HAPP.
Methods: We measured the plasma levels of endothelin-1 (ET-1), interleukin-1
beta (IL-1-beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha),
in 20 consecutive HAPP patients. Diagnosis of HAPP was based on the criteria
established by National Heart and Lung and Blood Institute Primary Pulmonary
Hypertension Registry Twenty age- and CD4 count-cross-matched HIV-positive
patients without HAPP were selected as controls. No patients of both groups had
known causes of increase of ET-1 and of other cytokines, such as diabetes, systemic hypertension, sepsis, or renal failure.
Results: Significant ET-1 and IL-6 plasma levels were found among HAPP patients than controls [6.0 ~3 pg/ml vs 1.0+0.1 pg/ml for ET-1 (p<0.001), and
0.82~0.03 vs 0.2~0.03 for IL-6 (p<0.001), for cases and controls, respectively].
On the contrary, no significant difference of IL-1-beta and TNF-alpha plasma
levels was found in the two groups [1.11~1.45 pg/ml vs 2.0+1.1 pg/ml for IL1-beta (p=0.8), and 2.6~3.0 pg/ml vs 2.2~2.5 pg/ml for TNF-alpha (p=0.6) for
cases and controls, respectively]. A positive correlation was found between ET1/IL-6 levels and values of pulmonary arterial pressure assessed by dopplerechocardiography (p<0.001). No correlation was found between ET-1/IL-6 and
HIV viral load (p=0.6) or CD4 count (p= 0.7).
Conclusions: A multifactorial hypothesis (alphal receptors' stimulation, genetic
factors, etc.) may be suggested in the pathogenesis of HAPP in HIV infection.
Presenting author: Nicola Petrosillo, INMI, Via Portuense, 292, 00149 Rome,
Italy, Tel.: [phone], Fax: [phone], E-mail: [email protected]
WePeA5796 Oncostatin-M production is associated to
neurological abnormalities in HIV infection
M. Dalessandro. Clinica malattie Infettive, Osp. "SS Annunziata", Via dei Vestini,
66013 Chieti sca/o (CH), Italy
Background: HIV-related nervous system involvement is characterized by brain
atrophy, ventricular dilatation, perivascular inflammation, astrocytosis and neuronal loss. Many of these features are not directly related to central nervous system (CNS) invasion by HIV, and some data suggest that an overproduction of
inflammatory substances by microglia, monocytes and macrophages takes place
in the CNS. Several of these mediators (TNF, NO, IL-6) can directly induce neuronal apoptosis. Recently Ensoli et al. have found that oncostatin-M (OM) seems
to be associated to neurodegeneration during HIV infection.
Methods: We investigated the role of this cytokine in 21 HIV+ patients (5 with
neurological involvement) and 15 HIV- controls. Briefly, OM was detected in 48 -hrs PBMC culture surnatants by ELISA (R&D Systems, Minneapolis, MN) either
unstimulated or stimulated with PHA, LPS or anti-CD3. Production of IFN-gamma
and IL-4, expression of CD3, CD4, CD8, CD56, and HIV-RNA were also determined and a brain TC was performed.
Results: Spontaneous release by cell cultures from neuro-HIV patients
(263 pg/mL, p<0.02) was stastically higher than in 16 HIV+ patients, both
CD4>500(17.5 pg/mL; mean CD4 994/mmc) and CD4< 500(84.4 pg/mL; mean
CD4 332/mmc) and HIV- subjects (16 pg/mL). Soluble mediators relase after stimulation were greater in stimulated cultures with PHA and anti-CD3, but similar
after LPS stimulation. Neuro-HIV patients had a mean CD4 count of 542/mmc.
IFN-gamma production was similar in different groups but IL-4 production was
lower in neuro-HIV patients.
Conclusions: OM can act on embryonal and mature neuronal cells with a toxic
mechanism, so we suggest that its increased spontaneous release by PBMC from
neuro-HIV patients may be related to an overproduction in CNS, interacting with
other soluble mediators in the pathogenesis of brain damage during HIV infection.
This might contribute to neurological damage more than the direct cytopathic effect of HIV.
Presenting author: margherita dalessandro, Clinica malattie Infettive, Osp. "SS
Annunziata", Via dei Vestini, 66013 Chieti scalo (CH), Italy, Tel.: [phone],
Fax: [phone], E-mail: marghydale @virgilio.it
WePeA5797 Secretion of interleukin-1l by astrocytes mediates
endothelin-1 and tumor necrosis factor- effetcs
on human brain microvascular endothelial cell
permeability
N. Didier1, l.A. Romero2, C. Creminion3, A. Mabondzo3. 1University Paris XI,
drm/dsv/sp, cea saclay 91191 gif sur yvette cedex, France; 2Open University,

Milton Keynes, United Kingdom; 3CEA-SPI-Saclay Gif su Yvette, France
Rational and Purpose:
Evidence suggests that endothelin (ET-1) plays an essential role in brain inflammation. Howevrer, whether ET-1 contributes directly to blood-brain barrier (BBB)
breakdown remains to be elucidated. Since the release of ET-1 could be modulate by the inflammatory cytokines, we investigated the expression of ET-1 upon
stimulation with TNFalpa by the brain endothelial cells (EC). In addition, the study