Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

276 Abstracts 21186-21191

12th World AIDS Conference

obtained in cultures of MDDC where dramatic inhibition of HIV replication could be
detected in the presence of rlL-16. The effect was found to be independant of the
induction of HIV-suppressing chemokines (MIP- la, MIP-1f and RANTES) and of
the inhibition of HIV-enhancing cytokines (TNF-a and IL-6). Using flow cytometry
analysis, rlL-16 appeared to down regulate CD4 expression in macrophages but
not in T cells.
Conclusion: The chemoattractant cytokine IL-16 possess potent HIV-suppressing activity in reservoir cells as well as in T lymphocytes. This activity is
found to be independant of the release of HIV-suppressing chemokines but to
be mediated by the regulation of viral transcription. These findings support the
potential use of rlL-16 in the treatment of HIV disease.
|21186 1Factors defining speed of HIV-infection progress
Lioudmila Siziakind, Andrei Shemshurd, J.V. Shestakova. Rostov Medical
University Immunol. Dept. Rostov-on-Don, Budjennovsky 72 Apt 17
Rostov-On-Don 344018, Russia
Objective: The study of speed dependence of infectious process progressing in
formation of various HIV-infections upon immunogenetic determination, monokins
production and virus genome variability.
Design: Prospective, controlled study.
Methods: 32 HIV-infected children aged 3-11 infected at one and the same
time in nosocomial niduses with HIV subtype G were examined. With the help
of ELISA the amount of IL-le and TNF, in blood serum and in mnonuclear
supernatants was determined. HLA-typing was done in microcytotoxic test in
Tarasaki modification and degree of virus genome variability was studied with
nested-PCR followed by sequencing of V3 gp 120 HIV loop and analysis of
achieved nucleotide sequences.
Results: In the group with fast progressing HIV-infection (the period of generalized lymphadenopathy stage less than 1 year) monocytes produced higher,
in comparison with slow progressing group IL-1% (218 pcg/ml and 44pcg/ml correspondingly) and TNF a (420 pcg/ml and 110 pcg/ml correspondingly) levels.
Growing deficiency of stimulated production IL -lp was observed. Noticed more
expressive variability of V3 gp 120 loop, when disease developed fast (Kv = 3.2
and 2.4 correspondingly), indirectly reflected growth of virus replication. Found
regularities in case of fast progress were associated at our patients with antigens
HLA: A3 (RR-2.8); A10 (RR-2.0), phenotype A2, A10 (RR-7.5); haplotype All,
B8 (RR-19.8); but in case of slow progress: Al (RR-2.7); All (RR-2.0); B15
(RR-7.5); B17 (RR-13.2); B27 (RR-20.9); DR4 (RR-3.6); DR6 (RR-2.5); A2, B8
(RR-19.8).
Conclusion: Phenotype HLA is a defining factor in development of fast or slow
course of HIV-infection, it defines intensity of monokins production and degree of
virus genome variability.
21187 Changes in serum interleukin-16 (IL-16) levels during the
course of HIV-1 infection
Edith Darcissacs, C. Amiel1, Y. Mouton2, M.R.A. Loyens1, A. Capron1,
G.M. Bahr1. 1 nstitut Pasteur de Lille, INSERM U167, 1 Rue PR. Calmette, BP
245 Lille 59019; 2Centre Hospitalier de Tourcoing, Tourcoing, France
Objectives: IL-16 is a chemoattractant cytokine with inhibitory effects on HIV
replication. To investigate a potential role of this cytokine in maintaining the
asymptomatic stage following HIV1 infection, circulating levels of IL-16 were
evaluated in HIV patients during the different clinical stages of the disease.
Subjects and Methods: 111 HIV1-infected subjects were included; 44 were
asymptomatic category A (mean CD4 = 574/mm3; median viral load (VL) = 1152
copies/ml), 34 were symptomatic category B (CD4 = 475; VL = 4243), and 35
were AIDS cases category C (CD4 = 190; VL = 7610). An additional group of 35
seronegative healthy volunteers was included. Titrations were performed by an
ELISA.
Results: Significant elevation in serum IL-16 was observed only in asymptomatic subjects (350 ~ 40 pg/ml) whereas symptomatics and AIDS patients
presented comparable levels to those of seronegative controls. More interesting
was the evolution of IL-16 levels in samples obtained from the same individuals
at different time intervals (1-8 years): throughout the asymptomatic period of
infection, there was a consistent elevation in serum IL-16. However, in samples
from asymptomatics or even symptomatics who progressed to AIDS, the IL-16
levels were found to drop significantly upon disease progression. This profile of
circulating IL-16 was found to occur independently of the evolution in CD4 counts,
viral load or antiretroviral therapy.
Conclusion: The maintained elevation in serum IL-16 during the asymptomatic
stage may well reflect a sustained antiviral response and could have a potential
value in monitoring absence of disease progression.
21188 Production of monokines in peripheral blood
mononuclear cells of the patients infected with human
immunodeficiency virus

Masahiko Ito1, Limin He1, H. Terunuma1, R. Yang1, F. Tanabe1, H. Hanafusa2,
N. Chiba1, A. Iwamotp1. Tamaho-Cho, Yamanashi Med. Univ. Yamnashi
409-3898; 20gikubo Hospital Tokyo, Japan
Objectives: To evaluate monokine-production in peripheral blood mononuclear
cells (PBMC) of the patients infected with human immunodeficiency virus type-1
(HIV-1).

Methods: PBMC were isolated by heparinized blood from healthy HIV-seronegative individuals, HIV-seropositive non-hemophilia individuals, and hemophiliacs
with or without HIV infection. The several levels of cytokines such as interleukin-12
(IL-12), IL-10, IL-6, 1L-1 beta and tumor necrosis factor (TNF)-alpha produced
by the PBMC stimulated with Staphylococcus aureus Cowan 1 strain (SAC)
and plasma transforming growth factor (TGF)-beta 1 levels were measured from
culture supernatants using specific ELISA systems.
Results: We demonstrated that IL-12 production in the HIV-infected patients
was significantly lower than that in healthy donors, and that IL-lbeta production of HIV seropositive hemophiliacs decreased compared with that of other
groups. In contrast, plasma level of TGF-beta 1 increased among HIV-infected
individuals, and IL-10, IL-6, production was enhanced with only HIV seropositive
hemophiliacs.
Conclusion: We demonstrated that the production of Thl inducible cytokine
such as IL-12 was down-regulated and Th2 related cytokines such as IL-10 and
IL-6 were up-regulated among HIV-infected indiviuals. It suggests that dysregulation of monokine production in PBMC of patients with HIV infection may explain
the dysfunction of cellular immunity among AIDS patients.
21189 Regulation of macrophage inflammatory protein-1 a
(MIP 1 a) in mononuclear cells by mycobacterium
tuberculosis during active pulmonary tuberculosis
infection
Harriet Mayanja-Kizza. Dept. of Medicine PO. Box 7072, Kampala, Uganda
Objective: MIP-la leads to decreased HIV-1 entry into cells by blocking the
HIV-1 coreceptor CCR5 which has affinity for macrophage tropic strains of HIV-1.
In people with HIV-1 infection, pulmonary tuberculosis (PTB) has been shown to
worsen HIV vireamia, and predispose to increased HIV associated mortality and
morbidity.
This study examines whether pulmonary tuberculosis (PTB) affects MIP-1a as
one mode of worsening HIV load in dually infected persons.
Design: Non matched case control study, with consecutive sampling.
Methods: Adult HIV negative patients with PTB, and PPD reactive HIV negative control subjects withnon TB chest conditions were recruited. Peripheral blood
mononuclear cells (PBMC) were separated from whole heparinized blood, and
stimulated with a nonvirulent MTB, H37Ra. Supernatants were collected at 3, 6,
24 and 120 hours, and MIP1 cc levels were assayed by ELISA kit.
Results: MTB upregulated MIP-la in cells from persons with HIV/PTB and
control subjects, but with different kinetics. There was a higher MIP a mean
level at 3 and 6 hours after H37Ra stimulation of cells from the control subjects
compared to the PTB patients. This peaked at 24 hours in the control subjects,
and at 120 hours in the PTB patients
Conclusion: It appears that there is less upregulation of MIP-la in TB HIV
negative patients compared to non TB HIV negative subjects. This lowered expression of MIP-la in PTB infection may in part contribute to the increased HIV
vireamia observed in dually infected HIV/PTB persons.
|21190 The associations between production of chemotactic
cytokines and immune function in children with HIV
Adriana Rosca'12, R. Costa3. 1Circumvalatiunii, 29 bl 13 ap 51 etaj 3, 1900
Timisoara; 2Institute of Public Health, Timisoara; 3Louis Turcanu Hospital,
Timisoara, Romania
Objective: To determine if the serum levels of RANTES and macrophage inflammatory proteine type 1 (MIP-1 alpha and MIP-1 beta) are correlated with soluble
CD4 and immune suppressive stages of the AIDS disease.
Material and Methods: We studied a cohort of 79 children which have been
hospitalized between June 1996 to March 1997 in the Paediatric Sector of the
Louis Turcanu Hospital-Timisoara, Romania. Majority of the infected children has
been born before 1990, especially in 1988 and 1989 and they have had an horizontal transmission. The determination of the soluble CD4 and of the MIP-1 alpha
and MIP-1 beta and RANTES chemokines has been made in the Immunological
Laboratory of Heidelberg by using the ELISA method.
Results: This study shows significant higher levels of RANTES but not MIP-1
alpha and MIP-1 beta proteins in response to HIV infection. The coefficient of
the liniar correlation shows an insignificant correlation between the soluble CD4,
the immune suppressive stages of the AIDS disease and the serum levels of
chemokines, (r = 0.8225, p = 0.3852 for RANTES; r = 0.948, p = 0.20 for MIP-1
alpha; r = 0.97, p = 0.1344 for MIP-1 beta).
Conclusion: Production of MIP-1 alpha, MIP-1 beta and RANTES chemokines
couldn't be correlated with immune stages of the AIDS disease, but their values
declined in parallel with reducing immune function.
21191 Levels of IL-2 and slL-2R in lymphocyte cultures from
patients receiving antiretroviral therapy
Velislava Terzieva, S.H. Raleva, L.Z. Froloshka, R.K. Markova. Natl. Ref. AIDS

Lab, 44A Stoletov Str. 1233 Sofia, Bulgaria
Objective: To study IL-2/slL-2R production and to correlate them with spontaneous lymphocyte proliferation/SLP/in patients receiving antiretroviral therapy.
Methods: Lymphocytes/Ly/from 4 Bulgarian HIV infected patients (stage
A1-C3) receiving AZT + 3TC were stimulated in vitro for 24 hours with PHA
and 144 h with HIV-1 antigen. CD4+, CD8+ and CD3+ counts were analysed by