Both HIV-1 infection and iron overload are independently associated with infection by Mycobacterium tuberculosis due to impaired macrophage function. A prospective study of in vitro assessment of macrophage function w...Both HIV-1 infection and iron overload are independently associated with infection by Mycobacterium tuberculosis due to impaired macrophage function. A prospective study of in vitro assessment of macrophage function was undertaken in a group of asymptomatic HIV-1 infected remunerated (professional) blood donors with (n = 54) or without (n = 54) prevalent practice of oral iron intake (subgroups I and II respectively). The assessment was carried out at enrolment as well as at the point of development of AIDS related illness (ARI). The subgroup I showed higher levels of pro-inflammatory cytokines viz. IL-1β, IL-6 and IL-8, but lowered levels of IL-12p70 in serum as well as in supernatant of monocyte derived macrophage (MDM) cultures both at enrolment and at the point of development of ARI in the subset of cases that developed pulmonary tuberculosis (PT) on follow up compared to the subset that developed categories of ARI other than pulmonary tuberculosis (non-PT) on follow up. The subgroup II of HIV-1 positive donors did not show any such alterations at enrolment or at the point of development of PT or non-PT categories of ARI on follow up. There was significant depression of nitrite level in serum as well as that produced by MDM culture at enrolment in subgroup I regardless of category of ARI developed on follow up while in subgroup II there was significant elevation in these levels at enrolment, more among cases developing PT than those developing non-PT category of ARI. The subgroup I demonstrated increased production of superoxide at enrolment. The present study suggested that depressed production of nitrite and IL-12p70 by macrophages induced by iron overload may be responsible for greater susceptibility of HIV-1 positive donors to M. tuberculosis while superoxide may be a less powerful anti-mycobacterial tool.展开更多
文摘Both HIV-1 infection and iron overload are independently associated with infection by Mycobacterium tuberculosis due to impaired macrophage function. A prospective study of in vitro assessment of macrophage function was undertaken in a group of asymptomatic HIV-1 infected remunerated (professional) blood donors with (n = 54) or without (n = 54) prevalent practice of oral iron intake (subgroups I and II respectively). The assessment was carried out at enrolment as well as at the point of development of AIDS related illness (ARI). The subgroup I showed higher levels of pro-inflammatory cytokines viz. IL-1β, IL-6 and IL-8, but lowered levels of IL-12p70 in serum as well as in supernatant of monocyte derived macrophage (MDM) cultures both at enrolment and at the point of development of ARI in the subset of cases that developed pulmonary tuberculosis (PT) on follow up compared to the subset that developed categories of ARI other than pulmonary tuberculosis (non-PT) on follow up. The subgroup II of HIV-1 positive donors did not show any such alterations at enrolment or at the point of development of PT or non-PT categories of ARI on follow up. There was significant depression of nitrite level in serum as well as that produced by MDM culture at enrolment in subgroup I regardless of category of ARI developed on follow up while in subgroup II there was significant elevation in these levels at enrolment, more among cases developing PT than those developing non-PT category of ARI. The subgroup I demonstrated increased production of superoxide at enrolment. The present study suggested that depressed production of nitrite and IL-12p70 by macrophages induced by iron overload may be responsible for greater susceptibility of HIV-1 positive donors to M. tuberculosis while superoxide may be a less powerful anti-mycobacterial tool.
