Enhanced Interleukin-1β, Interleukin-6 and Tumor Necrosis Factor-α Production by LPS Stimulated Human Monocytes Isolated from HIV + Patients

Abstract

Periodontal disease and tooth loss is a common finding among advanced HIV+ patients. In addition to local oral lipopolysaccharide (LPS) stimulation, systemic up-regulation of monocyte pro-inflammatory cytokine secretion may also be involved in the pathogenesis of HIV disease. A study was undertaken to investigate IL-1β, IL-6 and TNF-α production by resting and LPS stimulated monocytes isolated from HIV + patients and also to investigate the relationship of the patient's HIV viral load status to the cytokine production. Whole blood samples in EDTA were collected from 39 HIV-1 infected patients and 20 age and sex matched uninfected controls. Plasma was separated by centrifugation. Viral load was determined using a quantitative RT-PCR. Monocytes were isolated by Ficoll-hypaque gradient separation followed by overnight plastic adherence. Cultured monocytes (1 × 10⁶ml) were stimulated with LPS (1 μg/ml) of either P. gingivalis or F. nucleatum for 2, 8, 24 and 48 h and supernatant fluids were collected. IL-1β, IL-6, and TNF-α levels in supernatant fluids were estimated by ELISA. Increased overall production of IL-1β, IL-6 and TNF-α by LPS stimulated monocytes isolated from HIV-1 infected patients was observed when compared to HIV-1 uninfected controls. LPS stimulated monocytes from HIV-1 infected patients with high viral load (HVL) produced significant (p<0.05) elevations in these pro-inflammatory cytokines when compared to HIV-1 uninfected controls. Both LPS of P. gingivalis and F. nucleatum produced a comparable cytokine production by monocytes after 8 h of stimulation. These data suggest that enhanced IL-1β, IL-6 and TNF-α is produced by monocytes/macrophages isolated from HVL HIV + patients and may be involved in the overall pathogenesis of HIV-1 infection.