Loss of the CD56hi
CD16−
 NK cell subset and NK cell interferon-γ
 production during antiretroviral therapy for HIV-1: partial recovery by human growth hormone

SUMMARY Twenty-one rabbits were hypophysectomized during the second week of lactation. Hypophysectomy inhibited milk secretion within 3–7 days. Restoration of the milk yield to pre-operative levels was obtained when daily injections of either sheep prolactin (50 or 100 i.u.) or human growth hormone (HGH) (2·5 or 5 mg.) were administered; partial recovery of the milk yield was obtained with 25 i.u. sheep prolactin/day or 1·25 mg. HGH/day. Neither bovine growth hormone (BGH), adrenocorticotrophin (ACTH) nor cortisol acetate had any significant restorative effects on milk secretion or synergistic effects when combined with sheep prolactin or HGH. The probable development of immune responses to sheep prolactin and HGH was observed. After hypophysectomy, changes in milk composition were found which were similar in trend to the more gradual normal changes observed in late lactation. Sheep prolactin and HGH restored the composition of the milk as well as the yields to normal levels, and both hormones caused rapid increases in lactose yields. The pigeon crop-stimulating potency of the HGH preparation was low (equivalent to 3·7 i.u. sheep prolactin/mg.), yet its lactogenic and galactopoietic potencies were high thus emphasizing the unreliability of assessing the mammotrophic potencies of HGH preparations in birds.

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Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro

Blood ◽

10.1182/blood.v79.2.467.bloodjournal792467 ◽

1992 ◽

Vol 79 (2) ◽

pp. 467-472

Author(s):

J Laurence ◽

B Grimison ◽

A Gonenne

Keyword(s):

Growth Hormone ◽

Human Immunodeficiency Virus ◽

Viral Replication ◽

Human Growth Hormone ◽

Cellular Proliferation ◽

Recombinant Human Growth Hormone ◽

Human Growth ◽

Immunodeficiency Virus ◽

Hiv 1

Growth hormone (somatotropin) is a potent anabolic protein currently being evaluated clinically in cachexia associated with malignancy and human immunodeficiency virus (HIV) disease. Growth hormone can also lead to enhancement of lectin-mediated cellular proliferation, macrophage activation, and cytokine induction, events linked to induction of latent HIV in vitro. We thus explored the ability of recombinant human growth hormone (rhGH) to affect viral replication in acute and chronic HIV infection, and to alter transcription at the HIV- 1 long terminal repeat (LTR). A clone of promonocytic cells, chronically infected with HIV-1 and susceptible to viral induction by a variety of cytokines and protein kinase C activators, was unperturbed by rhGH used over broad concentrations (10 to 500 ng/mL) and time intervals. This unresponsiveness paralleled the lack of effect of rhGH on HIV-associated trans-activation in both monocytic and CD4+ T-cell lines. In contrast, rhGH enhanced viral replication in acutely infected peripheral blood mononuclear cells (PBMC) by twofold to 20-fold, albeit having no adverse effect on the antiviral efficacy of zidovudine (AZT). Augmentation of HIV growth correlated with stimulation of cellular DNA synthetic responses and an increase in tumor necrosis factor-alpha (TNF- alpha) secretion. These data are discussed in the context of ongoing clinical trials of rhGH in HIV-seropositive individuals with wasting syndromes.

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Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro

Blood ◽

10.1182/blood.v79.2.467.467 ◽

1992 ◽

Vol 79 (2) ◽

pp. 467-472 ◽

Cited By ~ 25

Author(s):

J Laurence ◽

B Grimison ◽

A Gonenne

Keyword(s):

Growth Hormone ◽

Human Immunodeficiency Virus ◽

Viral Replication ◽

Human Growth Hormone ◽

Cellular Proliferation ◽

Recombinant Human Growth Hormone ◽

Human Growth ◽

Immunodeficiency Virus ◽

Hiv 1

Abstract Growth hormone (somatotropin) is a potent anabolic protein currently being evaluated clinically in cachexia associated with malignancy and human immunodeficiency virus (HIV) disease. Growth hormone can also lead to enhancement of lectin-mediated cellular proliferation, macrophage activation, and cytokine induction, events linked to induction of latent HIV in vitro. We thus explored the ability of recombinant human growth hormone (rhGH) to affect viral replication in acute and chronic HIV infection, and to alter transcription at the HIV- 1 long terminal repeat (LTR). A clone of promonocytic cells, chronically infected with HIV-1 and susceptible to viral induction by a variety of cytokines and protein kinase C activators, was unperturbed by rhGH used over broad concentrations (10 to 500 ng/mL) and time intervals. This unresponsiveness paralleled the lack of effect of rhGH on HIV-associated trans-activation in both monocytic and CD4+ T-cell lines. In contrast, rhGH enhanced viral replication in acutely infected peripheral blood mononuclear cells (PBMC) by twofold to 20-fold, albeit having no adverse effect on the antiviral efficacy of zidovudine (AZT). Augmentation of HIV growth correlated with stimulation of cellular DNA synthetic responses and an increase in tumor necrosis factor-alpha (TNF- alpha) secretion. These data are discussed in the context of ongoing clinical trials of rhGH in HIV-seropositive individuals with wasting syndromes.

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Characterization of the defective interaction between a subset of natural killer cells and dendritic cells in HIV-1 infection

Journal of Experimental Medicine ◽

10.1084/jem.20060894 ◽

2006 ◽

Vol 203 (10) ◽

pp. 2339-2350 ◽

Cited By ~ 129

Author(s):

Domenico Mavilio ◽

Gabriella Lombardo ◽

Audrey Kinter ◽

Manuela Fogli ◽

Andrea La Sala ◽

...

Keyword(s):

Dendritic Cells ◽

Nk Cells ◽

Natural Killer ◽

Nk Cell ◽

Cell Subset ◽

Interferon Γ ◽

And Function ◽

Hiv 1

In this study, we demonstrate that the in vitro interactions between a CD56neg/CD16pos (CD56neg) subset of natural killer (NK) cells and autologous dendritic cells (DCs) from HIV-1–infected viremic but not aviremic individuals are markedly impaired and likely interfere with the development of an effective immune response. Among the defective interactions are abnormalities in the process of reciprocal NK–DC activation and maturation as well as a defect in the NK cell–mediated editing or elimination of immature DCs (iDCs). Notably, the lysis of mature DCs (mDCs) by autologous NK cells was highly impaired even after the complete masking of major histocompatibility complex I molecules, suggesting that the defective elimination of autologous iDCs is at the level of activating NK cell receptors. In this regard, the markedly impaired expression/secretion and function of NKp30 and TNF-related apoptosis-inducing ligand, particularly among the CD56neg NK cell subset, largely accounts for the highly defective NK cell–mediated lysis of autologous iDCs. Moreover, mDCs generated from HIV-1 viremic but not aviremic patients are substantially impaired in their ability to secrete interleukin (IL)-10 and -12 and to prime the proliferation of neighboring autologous NK cells, which, in turn, fail to secrete adequate amounts of interferon-γ.

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