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Query: UMLS:C0001175 (AIDS)
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Growth hormone and prolactin are neuroendocrine hormones that exert numerous effects on immune system function and development. Several fundamental questions are addressed in this review. Do neuroendocrine hormones affect specific immune cell types? What is the physiological significance of these effects? Can these effects be exploited clinically? While it is clear that there are indeed significant interactions between the neuroendocrine and immune systems, there are relatively few examples with demonstrated physiological significance. Present studies indicate that growth hormone and prolactin may exert markedly different effects on immune cell types depending on their stage in differentiation. Recent emphasis has also been focussed on the use of these hormones or their antagonists clinically in the treatment of AIDS, cancer, and autoimmune disease states due to their pleiotropic effects and low toxicity after systemic administration. However, we do not yet have a clear picture of how the influence of neuroendocrine hormones may be used to favorably alter pathophysiologic processes affecting immune function and development.
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PMID:Effects of growth hormone and prolactin immune development and function. 759 16

The concept of a neuro-endocrine-immune axis was proposed more than 50 years ago. Growth hormone (GH), a central component of this axis has many functions at both a molecular and cellular level, including thymocyte proliferation, stimulation of the cytotoxic activity of natural killer cells and induction of lymphocyte proliferation. Binding of GH to its receptors on lymphocytes stimulates the production of insulin-like growth factor I (IGF-I), which mediates the effects of GH on cell proliferation. Other effects of GH on the immune system appear to be direct, such as priming monocytes for enhanced production of hydrogen peroxide in response to phorbol esters, and stimulating neutrophils to secrete superoxide anions associated with enhanced phagocytic activity. Many of the effects of GH are shared by IGF-I. Despite these observations, and the fact that GH is produced and secreted in immunological tissues such as the thymus and spleen, immune deficiency is not characteristic of GH deficiency in humans. The question remains as to whether GH and IGF-I could be used as immunotherapy. Currently, both agents have been used in adults to diminish wasting due to acquired immunodeficiency syndrome, and GH has been shown to stimulate CD8+ cell counts. However, they had little impact on CD4+ cell counts, which may be due to IGF-I and GH resistance in these individuals. The use of GH and IGF-I as immunotherapies merits further study.
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PMID:Effects of growth hormone and insulin-like growth factor I on T- and B-lymphocytes and immune function. 940 46

It is now largely established that the immune and neuroendocrine systems cross-talk by using similar ligands and receptors. In this context, the thymus-hypothalamus/pituitary axis can be regarded as a paradigm of connectivity in both normal and pathological conditions. For example, cytokines and thymic hormones modulate hypothalamic-pituitary functions: (a) interleukin (IL)-1 seems to upregulate the production of corticotropin-releasing factor and by adrenocorticotropin by hypothalamic neurons and pituitary cells, respectively; (b) thymulin enhances LH secretion. Conversely, a great deal of data strongly indicate that the hypothalamic-pituitary axis plays a role in the control of thymus physiology. Growth hormone (GH) for example, enhances thymulin secretion by thymic epithelial cells (TEC), both in vivo and in vitro, also increasing extracellular matrix-mediated TEC/thymocyte interactions. Additionally, gap junction-mediated cell coupling among TEC is upregulated by ACTH. In a second vein, it was shown that GH injections in aging mice increased total thymocyte numbers and the percentage of CD3-bearing cells, as well concanavalin-A mitogenic response and IL-6 production. In addition to mutual effects, thymus-pituitary similarities for cytokine and hormone production have been demonstrated. Cytokines such as IL-1, IL-2, IL-6, interferon-gamma, transforming growth factor-beta and others can be produced by hypothalamic and/or pituitary cells. Conversely, hormones including GH, PRL, LH, oxytocin, vasopressin and somatostatin can be produced intrathymically. Moreover, receptors for various cytokines and hormones are expressed in both the thymus and the hypothalamus/pituitary axis. Lastly, it is noteworthy that a thymus-pituitary connectivity can also be seen under pathological situations. In this regard, an altered HPA axis has been reported in AIDS, human falciparum malaria and murine rabies, that also show a severe thymic atrophy.
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PMID:Immunoneuroendocrine connectivity: the paradigm of the thymus-hypothalamus/pituitary axis. 987 43

Although effective treatment of antiretroviral-associated metabolic abnormalities ultimately depends on understanding the mechanisms involved, clinicians facing these problems are beginning to feel compelled to do something now to manage treatment-related metabolic complications. Diet and exercise should not be overlooked, because both can be effective in managing these complications without causing further side effects. Fibric acid derivatives such as gemfibrozil and statins can lower HIV-associated cholesterol and triglyceride levels, although further data are needed on problematic interactions between statins and protease inhibitors (PIs). Hypoglycemic agents may have some role in managing glucose abnormalities, although troglitazone cannot be recommended for fat abnormalities alone and metformin may cause lactic acidosis. Growth hormone and anabolic steroids may have some role in treating lipodystrophy, but the cost of growth hormone is prohibitive for many patients and definitive data on efficacy are lacking. Replacing a PI with a reverse transcriptase inhibitor has improved lipid and glucose levels in some studies. However, that strategy begs the question of how the nucleosides might contribute to lipodystrophy.
AIDS Read 2000 Mar
PMID:How to manage metabolic complications of HIV therapy: what to do while we wait for answers. 1075 16

Growth hormone (GH) has been known to enhance immune responses, whether directly or through the insulin like growth factor-1, induced by GH. Recently a nonpeptidyl small m.w. compound, a GH secretagogue (GHS), was found to induce the production of GH by the pituitary gland. In this study, we examined 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 PBLs, 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 peripheral lymphocytes, but they exhibited a statistically significant increase in thymic cellularity and differentiation. When inoculated with a transplantable lymphoma cell line, EL4, the treated old mice showed statistically significant resistance to the initiation of tumors and the subsequent metastases. Generation of CTL to EL4 cells was also enhanced in the treated mice, suggesting that GHS has a considerable immune enhancing effect, particularly in the old mice. We have also found that GHS promoted better thymic engraftment in bone marrow transplant of SCID mice. We found more cycling cells in the spleens of treated mice, suggesting that GHS may exert its immune enhancing effect by promoting cell division in lymphoid cells. These observations ascribe to GHS a novel therapy possible for aging, AIDS, and transplant individuals, whose immune functions are compromised.
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PMID:Immune enhancing effect of a growth hormone secretagogue. 1123 71

The Food and Drug Administration (FDA) has approved Serostim, a human growth hormone, for use in AIDS clinical trials involving AIDS patients with uncontrolled and unintended weight loss. Previous studies have shown weight gains with the use of Serostim. The drug tends to increase lean body mass as opposed to fat, but it has shown no benefit in slowing the disease progression of AIDS. The drug is expensive, costing $12,600 for a single 12 week course of therapy. Serano Laboratories, Serostim's manufacturer, has applied to the FDA for approval. More information can be obtained by calling Serano Laboratories at (800)714-AIDS.
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PMID:New drug to treat wasting syndrome. 1136 44

MediCal will now provide reimbursement for the recombinant human growth hormone (Serostim) from Serono Laboratories through an Food and Drug Administration (FDA)-sanctioned Treatment Investigational New Drug program. The drug has shown promise in the treatment of AIDS-related wasting. California has appropriated $10 million for Serostim for MediCal clients. Patients qualify to receive the drug if they have failed either Megace or Marinol. Patient reimbursement advocacy activities and the distribution of Serostim are now handled by Stadtlanders Pharmacy, a mail-order business that has high visibility among people living with HIV infection and AIDS.
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PMID:Wider access to human growth hormone. 1136 98

The Food and Drug Administration's (FDA's) Endocrinologic and Metabolic Drugs Advisory Committee voted not to approve Serostim for AIDS-related wasting syndrome. Serostim is Serono Laboratories' recombinant human growth hormone. Committee members were concerned with the high required dosage, which has led to irreversible side effects in children who often use the drug for years. In its presentation to the committee, Serono did not present data on safety, toxicity, effects of long-term usage, or the frequency of necessary dosage reductions. Cost issues are being negotiated now; Serostim is expected to cost up to $100,000 per year. Serono will address some of the concerns in a later presentation and may be able to gain Serostim approval in some form.
AIDS Treat News 1996 Mar 15
PMID:Human growth hormone not recommended for approval on narrow advisory panel vote. 1136 1

Serono Laboratories, Inc. has recently been given accelerated Food and Drug Administration (FDA) approval for Serostim, a recombinant human growth hormone genetically engineered from mammalian cells, for treatment of AIDS-related wasting. While the price has not been established, Serono has agreed to a price cap under which no patient will be charged more than $36,000 per calendar year for the drug. Treatment activists played a critical role in getting the human growth hormone approved and available for AIDS patients. The historical background of this activism is detailed, revealing multiple efforts in making the drug more accessible despite barriers restricting its availability, and the pressure used on both the FDA and Serono to reach a compromise on the approval process.
AIDS Treat News 1996 Sep 06
PMID:Human growth hormone approved for wasting. 1136 17

The Food and Drug Administration (FDA) has given a verbal commitment to accelerated approval for recombinant human growth hormone (Serostim) for AIDS-associated wasting syndrome. The drug, manufactured by Serono Laboratories, is the first of its kind that directly affects the metabolic dysfunction of AIDS-related wasting. The approval came on the heels of a meeting with AIDS activists, Serono Laboratories, and the FDA. Serono committed, at the meeting's conclusion, to submit finalized documents to the FDA within a week. ACT UP Golden Gate won a victory when the wholesale price cap of the drug was set at $36,000.00 annually, despite the company's original demand of $75,000.00 or more.
Crit Path AIDS Proj 1996
PMID:AIDS activists secure approval for human growth hormone (Serostim). 1136 32


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