Fat redistribution in HIV-infected patients. A new hormonal-immune disorder?

Multidrug antiretroviral regimes in HIV-infected patients may have side effects. The most frequent side effects are changes in fat metabolism and distribution. We describe a particular pattern of fat redistribution (FR), characterized by a progressive enlargement of breast and abdominal girth and fat loss in the lower limbs, which occurs in approximately 10% of HIV-infected women treated with combined antiretroviral therapy. To elucidate the metabolic, endocrine, and immunologic consequences of the observed disturbance, we measured serum lipids, glucose, C-peptide, ACTH, plasma, urinary cortisol, and cytokines IL-2, IFN gamma, Il-4, IL-10, Il-12, and TNF alpha in 36 patients with FR and in a control group without FR. There were no significant differences in hormonal and metabolic laboratory testing between the two groups. Immunology studies showed that in vitro production of TNF alpha and IL-10 was lower and IL-12 production higher in SR patients. Whether or not such immune alterations may be reponsible or be caused by fat redistribution remains to be explained. One year after the follow up, 50% of the patients treated with triple therapy developed lipodystrophy, characterized by weight loss, face-wasting, and hyperglycemia; the remaining 50% remained unchanged. In 13 patients the 3TC withdrawal was followed by improvements of the syndrome in 50% and of lipodystrophy in about 25%. These data suggest that the FR syndrome is frequent in patients treated with 3TC and that it is associated with characteristic changes in the cytokine production

Immunoendocrinologic abnormalities in human immunodeficiency virus infection

Alterations in the production of adrenal steroids and a complex pattern of dysregulation in cytokine profiles accompany the progression of HIV infection. Cortisol levels increase in HIV infection, while those of dehydroepiandrosterone (DHEA), a physiologic antagonist of the immunoregulatory activities of cortisol, decrease. A shift from type-1 to type-2 cytokine production is also detected in most patients during disease progression. This shift is summarized as a defective production of interferon gamma (IFN gamma), interleukin-2 (IL), and IL-12 accompained by increased production of IL-4, IL-5, IL-6, and IL-10. IFN gamma and IL-2 are suppressed, while the generation of IL-4 is stimulated by cortisol and pharmacological doses of glucocorticoids (GC). GC and IL-4 stimulate the differentiation of B lymphocytes into IgE-producing plasma cells, the concentration of which augments in HIV infection. Finally, GC induces programmed cell death (PCD) in a variety of different cells, including mature T lymphocytes. Because (1) TH1 but not TH2 undergo rapid Fas-mediated PCD upon antigen-stimulation, and (2) TH2 clones preferentially survive in vitro cell cultures, the progressive shift from type-1 to type-2 cytokine production observed in HIV infection could be at least partially provoked by the increase in the production of cortisol and the reduction of DHEA. Progression of HIV infection to AIDS can be controlled by highly active antiretroviral therapy (HAART); HAART drastically reduces HIV plasma viremia, but is less effective in immune reconstitution. Additionally HAART is associated in a sizable portion of patients by complex lypodistropyc phenomena that often involve the endocrine system

Alpha 1 adrenoceptor subtype mediates noradrenaline induced contraction of the human internal mammary artery: radioligand and functional studies

The aim was to evaluate the characteristics of alpha adrenergic binding sites on human internal mammary arteries and the alpha adrenoceptor mediated vasoconstrictor response to catecholamines

Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy

To investigate the prevalence, metabolic features and risk factors of a particular pattern of fat redistribution (FR), characterized by a progressive enlargement of breast and abdominal girth associated with a wasting of the lower limbs, observed in HIV-infected women treated with combined antiretroviral (ARV) therapy

Cytokine production in women with antiretroviral treatment-associated breast fat accumulation and limb wasting

Objective: To test the cytokine production of peripheral blood mononuclear cells in a group of HIV-infected women with breast enlargement and lower limb wasting while receiving antiretroviral therapy (ART) including a protease inhibitor. Design: Case–control study including 20 women with fat tissue alterations and 20 matched controls treated with comparable ART. Methods: Adipose tissue alterations (ATA) were defined by increased breast size (> 2 bra sizes) accompanied by lower limb fat wasting. A randomly selected subset of patients underwent analyses including: dual energy X-ray absorptiometry, metabolic and endocrine assays, in vitro cytokine production testing [interferon-ª, interleukin (IL)-2, IL-4, IL10, IL-12, tumor necrosis factor-Æ (TNF-Æ)] after appropriate stimulation; T-cell phenotyping, T-helper function after stimulation with either tetanus toxoid, influenza antigen, allogeneic peripheral blood lymphocytes, and phytohemagglutinin. Endocrinological study included the determination of plasma concentrations of prolactin, growth hormone, testosterone, adrenocorticotropic hormone, cortisol and C-peptide. Results: In vitro production of IL-12 was higher (P ¼ 0.0001), and TNF-Æ (P ¼ 0.0093) and IL-10 (P , 0.0001) production were lower in stimulated peripheral blood mononuclear cells of ATA-positive women compared with ATA-negative women. ATApositive women also showed a better response to tetanus toxoid (P ¼ 0.021) and a lower median fluorescence intensity of CD14/DR (P ¼ 0.033). Plasma C-peptide values were higher in ATA-positive women compared with ATA-negative women (P ¼ 0.033), even if in the normal range (, 4 ng/ml) in all but one of the ATA-positive patients. Conclusion: HIV-1-infected women who developed breast enlargement and lower limb fat wasting while receiving ART had a favorable immunological profile with efficient IL-12 production and T-helper function, and with TNF-Æ production in the range of a HIV-negative reference population. These findings suggest that the rescue of some immune functions under ART may be involved in the pathogenesis of this particular adipose tissue disorde

Cytokine production in women with antiretroviral treatment-associated breast fat accumulation and limb wasting

Objective: To test the cytokine production of peripheral blood mononuclear cells in a group of HIV-infected women with breast enlargement and lower limb wasting while receiving antiretroviral therapy (ART) including a protease inhibitor. Design: Case–control study including 20 women with fat tissue alterations and 20 matched controls treated with comparable ART. Methods: Adipose tissue alterations (ATA) were defined by increased breast size (> 2 bra sizes) accompanied by lower limb fat wasting. A randomly selected subset of patients underwent analyses including: dual energy X-ray absorptiometry, metabolic and endocrine assays, in vitro cytokine production testing [interferon-ª, interleukin (IL)-2, IL-4, IL10, IL-12, tumor necrosis factor-Æ (TNF-Æ)] after appropriate stimulation; T-cell phenotyping, T-helper function after stimulation with either tetanus toxoid, influenza antigen, allogeneic peripheral blood lymphocytes, and phytohemagglutinin. Endocrinological study included the determination of plasma concentrations of prolactin, growth hormone, testosterone, adrenocorticotropic hormone, cortisol and C-peptide. Results: In vitro production of IL-12 was higher (P ¼ 0.0001), and TNF-Æ (P ¼ 0.0093) and IL-10 (P , 0.0001) production were lower in stimulated peripheral blood mononuclear cells of ATA-positive women compared with ATA-negative women. ATApositive women also showed a better response to tetanus toxoid (P ¼ 0.021) and a lower median fluorescence intensity of CD14/DR (P ¼ 0.033). Plasma C-peptide values were higher in ATA-positive women compared with ATA-negative women (P ¼ 0.033), even if in the normal range (, 4 ng/ml) in all but one of the ATA-positive patients. Conclusion: HIV-1-infected women who developed breast enlargement and lower limb fat wasting while receiving ART had a favorable immunological profile with efficient IL-12 production and T-helper function, and with TNF-Æ production in the range of a HIV-negative reference population. These findings suggest that the rescue of some immune functions under ART may be involved in the pathogenesis of this particular adipose tissue disorde