The effects of growth hormone and insulin-like growth factor I on the immune system of aged female monkeys

Abstract

The aging process is associated with a significant reduction in circulating GH and insulin-like growth factor I (IGF-I) levels. During this period, immune function also declines. Rodent data suggest that treatment with recombinant human GH (rhGH) or rhIGF-I enhances immune function in normal adult mice. To determine whether rhGH and/or rhIGF-I treatment could improve immune function in aged female rhesus monkeys, we administered rhIGF- I (120 μg/kg · day), rhGH (100 μg/kg · day), a combination of therapies, or excipient alone by sc infusion using Alzet pumps over a 7-week period. At 28 days, the pumps were replaced, and the animals were bled and immunized with tetanus toxoid. At the end of the 7-week period, the animals were killed. rhGH and rhIGF-I increased serum GH and IGF-I levels, respectively; rhGH and rhIGF-I in combination induced the highest serum IGF-I levels (906 ± 261 ng/ml vs. control, 185 ± 36 ng/ml at death). rhGH and rhIGF-I also increased IGFBP-3 levels. rhGH infusion resulted in the most marked changes in lymph node and splenic reactivity, as determined by histological assessment. Lymph nodes from the rhGH-treated animals showed changes from baseline indicating a stimulated reactive state. Both rhGH and rhIGF-I had effects on lymphocyte phenotype, but there were different responses in blood compared to spleen and lymph nodes. In the peripheral blood, the percent B cells and percent CD8 cell count rose after rhIGF-I therapy, with a fall in the CD4/CD8 ratio. In the spleen, on the other hand, the CD4/CD8 ratio nearly doubled (0.33 ± 0.12 vs. 0.53 ± 0.12) after rhIGF-I therapy. In the spleen, the combination of rhGH and rhIGF-I increased the percent T cells from 26.7 ± 2.3 to 42.4 ± 4.4 and the CD4/CD8 ratio to 0.71 ± 0.11. Both rhGH and rhIGF-I increased in vivo (antibody titer to tetanus toxoid) responses by lymphocytes, and rhGH increased Con-A-induced DNA synthesis in vitro. These results confirm the rodent data showing that rhGH and rhIGF-I cause beneficial changes in immune function and suggest that further investigation is warranted to assess their therapeutic potential.