Jd. Jacobson et al., Gonadotropin-releasing hormone increases CD4+-lymphocyte numbers in an animal model of immunodeficiency, J ALLERG CL, 104(3), 1999, pp. 653-658
Background: Gonadotropin-releasing hormone (GnRH) possesses immunostimulato
ry properties. We have previously demonstrated that GnRH antagonists decrea
se lymphocyte numbers in an animal model of autoimmune disease. We speculat
ed that the converse might be true, that GnRH administration would increase
lymphocyte numbers or alter lymphocyte subsets in an immunodeficiency stat
e.
Objective: Our purpose was to test the hypothesis that GnRH agonist would i
ncrease IgG and CD4 counts in a rat model of immunodeficiency independently
of gonadal steroids.
Methods: We used diabetes-prone (DP) BE rats. This model has been character
ized to have an AIDS-like lymphocyte profile, with lymphopenia and depresse
d CD4 counts. Ovariectomized female DP rats were randomized to receive subc
utaneous injections with GnRH or vehicle 6 times meekly. DR rats were ovari
ectomized and treated with vehicle as controls. We performed flow cytometri
c analysis and complete blood cell counts at baseline, 3.5 weeks, and 7 wee
ks of treatment. We also measured total serum IgG and luteinizing hormone l
evels. Results: GnRH administration significantly increased total serum IgG
levels in DP rats compared with vehicle. The percentages of CD4(+) cells i
n blood were also significantly increased in the GnRH-treated group compare
d with the vehicle-treated group and compared with baseline. Similarly, the
absolute numbers of CD4(+) positive T cells were increased over controls a
t 7 weeks. The effects of GnRH were specific for the CD4 subset because the
re were no significant differences in numbers of CD8(+) positive cells betw
een the 2 treatment groups.
Conclusion: GnRH shows potential utility as an immunostimulatory agent in i
mmunodeficient states manifesting diminished numbers of immunocompetent CD4
(+) T lymphocytes.