Enhanced interleukin-1 beta, interleukin-6 and tumor necrosis factor-alphaproduction by LPS stimulated human monocytes isolated from HIV+ patients

Periodontal disease and tooth loss is a common finding among advanced HIVpatients. In addition to local oral Lipopolysaccharide (LPS) stimulation sy stemic up-regulation of monocyte pro-inflammatory cytokine secretion may al so be involved in the pathogenesis of HIV disease. A study was undertaken t o investigate IL-1 beta, IL-6 and TNF-alpha production by resting and LPS s timulated monocytes isolated from HIV+ patients and also to investigate the relationship of the patient's HIV viral load status to the cytokine produc tion. Whole blood samples in EDTA were collected from 39 HIV-1 infected pat ients and 20 age and sex matched uninfected controls. Plasma was separated by centrifugation. Viral bad was determined using a quantitative RT-PCR. Mo nocytes were isolated by Ficoll-hypaque gradient separation followed by ove rnight plastic adherence. Cultured monocytes (1x10(6)/ml) were stimulated w ith LPS (1 mu g/ml) of either P. gingivalis or F. nucleatum for 2, 8, 24 an d 48 h and supernatant fluids were collected. IL-1 beta, IL-6, and TNF-alph a levels in supernatant fluids were estimated by ELISA. Increased overall p roduction of IL-1 beta, IL-6 and TNF-alpha by LPS stimulated monocytes isol ated from HIV-1 infected patients was observed when compared to HIV-1 uninf ected 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 LP S of P. gingivalis and F. nucleatum produced a comparable cytokine producti on by monocytes after 8 h of stimulation. These data suggest that enhanced IL-1 beta, IL-6 and TNF-alpha is produced by monocytes/macrophages isolated from HVL HIV+ patients and may be involved in the overall pathogenesis of HIV-1 infection.