Age-associated decline in immune system is believed to contribute to morbidity and mortality in elderly individuals due to increased incidence of infection, autoimmunity, and cancer. Thymic involution begins early in life, as young as one year of age, and continues throughout life. There has been considerable interest in developing means to either restore T cell production in the involuted thymus or delay its rate of decline. The link between the immune and endocrine systems was first proposed 75 years ago when thymic atrophy was observed in rats after hypophysectomies. A number of studies have supported a role for growth hormone (GH) on immune function and thymic growth. Early studies by Dr. Dan L. Longo and colleagues have shown GH to be a potential thymopoietic factor in Snell-Bagg (DW/J) mice by inducing thymic hyperplasia. GH has been shown to stimulate thymopoiesis in aged rodents by increasing both thymic size and cellularity. While the precise mechanism(s) involved in the thymotrophic effects of GH remains to be defined, several theories have suggested that GH increases the number of thymic progenitors recruited from the bone marrow to the thymus, hence promoting thymopoiesis. Despite a number of studies focusing on the effects of GH on thymic activity in rodents, little to no data currently exists on its effects in humans. We are interested in studying whether recombinant human GH (rhGH) can in fact stimulate thymic and immune functions in human. If so, the potential implication of using GH in treating people with diminished immune capacity such as the elderly is substantial. Clinical studies looking at the use of rhGH replacement in healthy aging adults had showed that GH increased lean body mass and decreased fat mass, but no significant change in bone mineral density was found. None of these studies, to our knowledge, looked closely at the immune system. Furthermore, there were significant adverse effects associated with these trials including edema, arthralgia, carpal tunnel syndrome, glucose intolerance, and even diabetes, making the benefits of GH replacement in healthy aging adults suspect. These adverse events associated with GH replacement may be due to the supraphysiologic dose of GH used in these trials, 20-30 mcg/kg per injection given 3 times a week (averaged of 8.6-12.9 mcg/kg/day) or the frequency of GH administration, 3 times a week to the most once a day which is again not physiologic. GH is secreted in pulsatile fashion by the pituitary in humans. The purpose of this study is to determine whether GH administration may elicit clinical significant and relevant changes in the human immune system. We also want to examine whether GH administered in a more physiologic fashion, i.e., multiple times a day versus once a day may elicit a more pronounce immune response with more favorable metabolic profiles and fewer side effects. We plan to study male subjects only at first because the GH dose requirement in male is lower. If the results from this study are promising, a similar study may be conducted in females in the future. We have finished recruitment and are in the process of data analysis.
| Makrogiannis, Sokratis; Ramachandran, Ramona; Fishbein, Kenneth W et al. (2011) Towards segmentation of the thymus in fat and water parametric MR images. Conf Proc IEEE Eng Med Biol Soc 2011:8078-81 |
