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M94A2500.TXT
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1994-10-25
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Document 2500
DOCN M94A2500
TI Serotonin reduces intracellular cAMP and restores the proliferative
capacity of T cells from HIV seropositive subjects.
DT 9412
AU Afzelius P; Hofmann B; Kronborg G; Iversen J; Nielsen JO; Dept. of
Infectious Diseases, Hvidovre University Hospital,; Copenhagen.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):29 (abstract no. 090A). Unique
Identifier : AIDSLINE ICA10/94370075
AB OBJECTIVE: To investigate whether serotonin could restore the
proliferative capacity of T cells from HIV seropositive subjects by
lowering intracellular levels of cAMP. We have earlier shown that part
of the T cell anergy in HIV infection is caused by an increase in
intracellular cAMP possibly caused by viral proteins (Hofmann et al
Proc. Nat. Acad. Sci. USA 1993). Also, we have shown that the
proliferative and cytotoxic capability could be restored by decreasing
the intracellular cAMP level in T lymphocytes from HIV seropositive
subjects with inhibitors of adenylate cyclase (Hofmann et al. AIDS
1993). Intracellular cAMP levels in lymphocytes can be down regulated by
stimulation of the 5HT1a serotonin receptor. METHODS: Lymphocyte
proliferative assay using PWM or tetanus as stimulators. RESULTS:
Addition of either serotonin (5HT) to cultures of T cells from HIV
seropositive subjects stimulated with either PWM or tetanus increased
the response with about 30% in 5 of 5 individuals. That this was a
direct serotonin effect was supported by obtaining similar results using
the specific 5HT1a agonist 8-hydroxy-2-(di-n-propylamino) tetralin.
DISCUSSION AND CONCLUSION: We have searched for physiological reagents
with the ability to lower the increased cAMP level in T cells from HIV
seropositive subjects. Serotonin and serotonin-related compounds are
candidates for clinical trials. Serotonin is currently being studied in
a phase 1 clinical trial.
DE Cell Division/*DRUG EFFECTS Cells, Cultured Cyclic AMP/*METABOLISM
Human HIV Seropositivity/*PHYSIOPATHOLOGY Serotonin/*PHARMACOLOGY
Serotonin Antagonists/PHARMACOLOGY T-Lymphocytes/DRUG
EFFECTS/*IMMUNOLOGY T-Lymphocytes, Cytotoxic/IMMUNOLOGY MEETING
ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).