Effects of subchronic d-fenfluramine on splenic immune functions in young and old male and female Fischer 344 rats.
The present study was designed to demonstrate age- and sex-related differences in immune functions, and to determine whether subchronic elevations in serotonin (5-HT) availability in vivo would alter immune functions assessed subsequently in vitro. Male and female F344 rats (5 and 21 months of age) were administered the 5-HT releaser and reuptake inhibitor, d-fenfluramine (d-Fen), in their drinking water for 30-38 days then killed. The young animals received a higher dose (1.8 mg/kg/day) of d-Fen than the old rats (0.6 mg/kg/day) in order to compensate for age-related decreases in drug biotransformation and clearance. Brain and spleen d-Fen and metabolite concentrations, however, were considerably higher in the young than in the old rats. d-Fen treatment did not affect body weight or fluid intake. Although substantial sex differences in immune function were not discerned, age-related decreases were observed in absolute splenic cellularity, recombinant interleukin-2 (rIL-2) stimulated natural killer (NK) cytotoxicity, LPS stimulated B-cell mitogenesis, and in the level of Ox19 (CD5) positive cells. d-Fen caused an increase in absolute spleen weight and a decrease in absolute splenic cellularity only in the old rats of both sexes. Spleen cells from young male and old female rats receiving d-Fen had relatively more large granular lymphocytes and enhanced baseline and rIL-2 activated killing of YAC-1 cells than their vehicle matched or opposite sex counterparts. The drug also increased Con A-induced T-cell proliferation in young males and LPS induced B-cell proliferation in old females. d-Fen decreased Ox39 (CD25) levels by 19%, but did not affect any of the other phenotypes examined. The results suggest that 5-HT has a selective stimulatory effect on young male and old female NK activity, and that old female rats are more sensitive to the immunological effects of d-Fen than old male rats.
Clancy
J
J
Department of Cell Biology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153.
Petrovic
L M
LM
Gordon
B H
BH
Handa
R J
RJ
Campbell
D B
DB
Lorens
S A
SA
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000494:pharmacology; D000375:Aging / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D005277:Fenfluramine / Q000493:pharmacokinetics / Q000494:pharmacology*; D007107:Immune System / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D005277:Fenfluramine