Abstract

A retrospective analysis on the assessment of the level of p65 component of the transcription factor Nuclear Factor Kappa B (NF-kB p65) in the nuclear extract of lipopolysaccharide stimulated peripheral blood mon-onuclear cells (PBMCs) of remunerated blood donors with HIV-1 infection revealed NF-kB p65 to be significantly higher in the subgroup with history of oral iron intake compared to the HIV-1 infected subgroup without such history. The level of NF-kB p65 in iron consuming subgroup of HIV-1 positive donors showed positive correlation with the serum ferritin level and with the rate of increase in viral load. The NF-kB p65 level also showed positive correlation with the level of superoxide produced by cultured Monocyte derived macrophages (MDMs) as well as with the levels of the immune activation markers viz. Tumour necrosis factor alpha (TNF-α) and two of its soluble markers i.e. Tumour necrosis factor receptor types one and two (TNFRI and TNFRII) reported in earlier studies in the same subgroup. The opposing roles of NF-kB in situation of iron overload in HIV-1 infection i.e. disease enhancement on one hand and facilitation of effective antiretroviral therapy through activation of HIV-1 in the latently infected cells on other hand suggest the need for further research to weigh benefits and risks of iron therapy in situations where iron deficiency in HIV-1 infection may be a serious consideration.

Highlights

  • There are numerous reports indicating enhancing effect of iron on disease progression in Human Immunodeficiency Virus type-1 (HIV-1) infection [1] [2] [3]

  • A retrospective analysis on the assessment of the level of p65 component of the transcription factor Nuclear Factor Kappa B (NF-kB p65) in the nuclear extract of lipopolysaccharide stimulated peripheral blood mononuclear cells (PBMCs) of remunerated blood donors with HIV-1 infection revealed NF-kB p65 level to be significantly higher in the subgroup with history of oral iron intake compared to the HIV-1 infected subgroup without such history

  • The NF-kB p65 level showed positive correlation with the level of superoxide produced by cultured Monocyte derived macrophages (MDMs) as well as with the levels of the immune activation markers viz. Tumour necrosis factor alpha (TNF-α) and two of its soluble markers i.e. Tumour necrosis factor receptor types one and two (TNFRI and TNFRII) reported in earlier studies in the same subgroup

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Summary

Introduction

There are numerous reports indicating enhancing effect of iron on disease progression in Human Immunodeficiency Virus type-1 (HIV-1) infection [1] [2] [3]. In the first part of the report, the iron consuming subgroup of HIV-1 positive donors showed high state of immune activation as evident from elevated serum levels of Tumor Necrosis Factor alpha (TNF-α) and two of its receptors viz. TNFRI (p55) and TNFRII (p75) the probable mechanism for such high immune activation was not explored [4]. The present report provides retrospective analysis of NF-κB p65 level in nuclear extracts of peripheral blood mononuclear cells (PBMCs) stimulated by Lipopolysaccharide (LPS) in the subgroups of asymptomatic HIV-1 positive blood donor with history of oral iron intake, in relation to reported levels of serum ferritin, rate of increase in HIV-1 viral load, superoxide produced by MDM culture and serum levels of the three immune activation markers viz. TNF-α, TNFRI and TNFRII [4] [5]

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