Growth hormone (GH) has been known to enhance immune responses, whether dir
ectly or through the insulin like growth factor-1, induced by GN. Recently
a nonpeptidyl small m.w. compound, a GH secretagogue (GHS), was found to in
duce the production of GH by the pituitary gland. In this study, we examine
d the effect of GHS in immunological functions of 5- to 6-wk-old and 16- to
24-month-old mice. In young mice, we observed a significant increase in PB
Ls, but T and B cell-proliferative responses were not consistently enhanced
, The old mice, treated with GHS for 3 wk, did not show increases in periph
eral lymphocytes, but they exhibited a statistically significant increase i
n thymic cellularity and differentiation, When inoculated with a transplant
able Lymphoma cell line, EL4, the treated old mice showed statistically sig
nificant resistance to the initiation of tumors and the subsequent metastas
es. Generation of CTL to EL4 cells was also enhanced in the treated mice, s
uggesting that GHS has a considerable immune enhancing effect, particularly
in the old mice. We have also found that GHS promoted better thymic engraf
tment in hone marrow transplant of SCID mice. We found more cycling cells i
n the spleens of treated mice, suggesting that GHS may exert its immune enh
ancing effect by promoting cell division in lymphoid cells. These observati
ons ascribe to GHS a novel therapy possible for aging, AIDS, and transplant
individuals, whose immune functions are compromised.