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

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