The effects of growth hormone and insulin-like growth factor I on the immune system of aged female monkeys.
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 micrograms/kg x day), rhGH (100 micrograms/kg x 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 ration 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.
LeRoith
D
D
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
Yanowski
J
J
Kaldjian
E P
EP
Jaffe
E S
ES
LeRoith
T
T
Purdue
K
K
Cooper
B D
BD
Pyle
R
R
Adler
W
W
D000367:Age Factors; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D005260:Female; D007107:Immune System / Q000187:drug effects*; D007260:Infusion Pumps; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000032:analysis; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008251:Macaca; D011994:Recombinant Proteins / Q000008:administration & dosage
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I