Growth hormone therapy and immune function

Abstract Multiple lines of evidence have documented interactions between the Growth Hormone/Insulin-Like Growth Factor axis and the Immune System. These interactions have been documented both in vitro and in vivo , both in animal models as well as in humans. We have been studying this interaction in children with growth hormone insufficiency. In the baseline state, we, and others, have shown that children with growth hormone deficiency do not have significantly altered immune functions. The total levels of white blood cells, as well as red blood cells as well as most immune parameters tend to be normal. During treatment with exogenous human growth hormone, total levels of white blood cells do not change significantly. We and others have shown that there is a significant decrease of percent B-cells during the course of treatment, which in most patients is transient. This has been shown during treatment with both pituitary derived growth hormone as well as biosynthetic human growth hormone. Of interest however, serum levels of immunoglobulin including immunoglobulin A, immunoglobulin M, and immunoglobulin G have remained normal. In some patients a substantial transient decrease in PHA responsiveness as well as a T-helper/suppressor ratio has also been described. In as much as most of the effects of exogenous human growth hormone treatment have affected B-cells we attempted to describe growth hormone receptors on circulating peripheral lymphocytes. By the use of two-color flow cytometry, we were able to report hat monocytes along with B-cells are the cells that exhibit growth hormone receptors. Growth hormone receptors on B-cells were normal in a variety of clinical conditions characterized by short stature in whom growth hormone receptors are expected to be normal. In preliminary studies, we have also been albe to examine the production of growth hormone by lymphocytes and were able to detect significant growth hormone levels produced by cells derived from even growth hormone deficient children. In vitro , numerous studies have shown that growth hormone as well as IGF-I can increase red blood cell production as well as increase the proliferation of leukemic cell lines. There has been a concern that some patients with growth hormone deficiency have developed leukemia during the course of growth hormone treatment. We have shown that several patients identified as having growth hormone deficiency who have not received any exogenous growth hormone also developed leukemia suggesting that the association between growth hormone treatment and leukemia is as best tenuous. In growth hormone deficient children and adults there has been a suggestion that acute institution of growth hormone therapy has lead to an increase in hemoglobin levels. We are in the process of studying the interaction between hemoglobin and insulin like growth factor I (an index of growth hormone production and treatment). In a series of more than 30 growth hormone deficient children treated for up to 8 years, we have found no significant association between Hemoglobin and IGF-I, suggesting that the effects of growth hormone on red blood cell production in children may be an acute adaptational effect which does not lead to a long-term association between the two parameters.