RESUMO
Heroin dependence may result in suppression of adaptive immune responses. Previously, we demonstrated an increase in relative numbers of inhibitory CD4+ regulatory T cells (Tregs) and impaired proliferative activity of CD4+ T cells from heroin-addicted patients in contrast to patients in opioid maintenance therapy and healthy controls. However, it remains elusive whether heroin has a direct impact on the CD4+ T cell compartment or whether observed effects result from stressful living conditions. Here, we analyzed the frequencies of Tregs and the proliferation as well as the cytokine production of stimulated CD4+ T cells from heroin-addicted patients with use of illicit heroin, patients in heroin-assisted treatment (HAT), and patients in methadone maintenance therapy (MMT). Relative numbers of CD4+ Tregs were significantly enhanced in patients with illicit heroin abuse compared with patients in HAT or MMT. Notably, CD4+ T cells from patients in HAT and from persons using illicit heroin showed significant reduced proliferation and secretion of the pro-inflammatory cytokines IFN-γ and IL-6 upon stimulation in vitro. From these results, we conclude that structured programs such as HAT and MMT dampen elevated frequencies of Tregs in heroin-addicted patients, whereas chronic heroin administration irrespective of using illicit heroin or receiving HAT has a direct impact on the proliferative activity and cytokine production of CD4+ T cells.
Assuntos
Proliferação de Células/efeitos dos fármacos , Dependência de Heroína/tratamento farmacológico , Heroína/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Analgésicos Opioides/uso terapêutico , Citocinas/efeitos dos fármacos , Feminino , Humanos , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos/métodosAssuntos
DNA Polimerase Dirigida por DNA/genética , Disartria/genética , Neuropatia Hereditária Motora e Sensorial/genética , Síndrome MELAS/genética , Oftalmoplegia/genética , Encéfalo/patologia , DNA Polimerase gama , Disartria/patologia , Feminino , Neuropatia Hereditária Motora e Sensorial/patologia , Humanos , Síndrome MELAS/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Oftalmoplegia/patologiaRESUMO
Although heterosexual and homosexual individuals clearly show differences in subjective response to heterosexual and homosexual sexual stimuli, the neurobiological processes underlying sexual orientation are largely unknown. We addressed the question whether the expected differences in subjective response to visual heterosexual and homosexual stimuli may be reflected in differences in brain activation pattern. Twenty-four healthy male volunteers, 12 heterosexuals and 12 homosexuals, were included in the study. BOLD signal was measured while subjects were viewing erotic videos of heterosexual and homosexual content. SPM02 was used for data analysis. Individual sexual arousal was assessed by subjective rating. As compared to viewing sexually neutral videos, viewing erotic videos led to a brain activation pattern characteristic for sexual arousal in both groups only when subjects were viewing videos of their respective sexual orientation. Particularly, activation in the hypothalamus, a key brain area in sexual function, was correlated with sexual arousal. Conversely, when viewing videos opposite to their sexual orientation both groups showed absent hypothalamic activation. Moreover, the activation pattern found in both groups suggests that stimuli of opposite sexual orientation triggered intense autonomic response and may be perceived, at least to some extent, as aversive.