Buspirone, a serotonin receptor agonist, increases CD4 T-cell counts and modulates the immune system in HIV-seropositive subjects.
OBJECTIVE
We have previously shown that drugs that decrease intracellular cAMP levels increase/restore the proliferative and cytotoxic capacity of T cells from HIV-seropositive subjects in vitro. Buspirone, a serotonin receptor agonist, indirectly decreases intracellular cAMP levels in T cells and has the same increasing/restoring effect on T-cell proliferation in lymphocytes from HIV-seropositive subjects in vitro.


METHODS
Buspirone was given as a single high dose to six HIV-seropositive subjects, or as continuous medication with increasing dosage over 6 weeks to nine HIV-seropositive subjects, with CD4 T-cell counts of 150-300 x 10(6)/l.


RESULTS
Significant increases in CD4 T cells, CD4 percentage and CD4/CD8 ratio were found 1 week after a single high dose of buspirone was administered. With continuous administration, a significant increase in CD4 T cells was observed after 1 and 4 weeks. Serum HIV RNA showed a significant decrease 1 h after a single dose of buspirone was administered. With continuous administration of buspirone, plasma HIV RNA first increased within the first 2 weeks of treatment and then decreased towards and below baseline concurrently with a significant decrease in CD8T cells. The proliferative T-cell response to poke weed mitogen and membrane expression of IL-2R increased significantly during continuous treatment with a significant decrease in expression of HLA-DR on CD8+ T cells. Development of "flu-like' symptoms, so severe that two patients withdrew from the study and two patients ceased medication before time, was a clinical indication of modulation of the immune system by buspirone.


CONCLUSIONS
The study shows that buspirone modulates the immune system and leads to changes in the CD4 and CD8 T-cell numbers, functional capacity, cell maturation and viral load.
Department of Clinical Immunology, Copenhagen University Hospitals, Hvidovre, Denmark.
B
B
Hofmann
P
P
Afzelius
J
J
Iversen
G
G
Kronborg
P
P
Aabech
T
T
Benfield
E
E
Dybkjaer
J O
JO
Nielsen
D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D002065:Buspirone / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000187:drug effects*; D016516:CD4-CD8 Ratio / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D012367:RNA, Viral / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000097:blood; D001613:beta 2-Microglobulin / Q000032:analysis
D012367:RNA, Viral; D015375:Receptors, Interleukin-2; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin; D002065:Buspirone