Evaluation of over the counter vaginal lubricants Nonoxynol-9 and KY Jelly as potential inducer of proinflammatory cytokines in human immune cells

Abstract

Topical microbicides such as Nonoxynol-9 (N9) and KY jelly have been used as vaginal microbicides in clinical trials as anti-HIV-1 products. The objective of this study was to determine if the use of these microbicides may cause production of proinflammatory cytokines in vitro. Such cytokines include, tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), interlukin-6 (IL-6), and Interlukin-8 (IL-8). Cellular viability was determined for the peripheral blood mononuclear cells (PBMCs) and Macrophages by culturing them for 24 hours in the presence of serial dilutions of product or placebo. Product and placebo dilutions that gave culture viabilities of ≥ 60% compared to control cultures were considered to be nontoxic. The non-toxic dilutions were 1:100 for KY jelly in both PBMCs and Macrophages. Whereas, the non-toxic dilutions were 1:1000 for N9 in both PBMCs and Macrophages. The values of IL1β, TNF-α, were 0.1 < 2.0 pg/mL for both PBMCs and macrophages. The levels of IL-8 ranged between 9-13 pg/mL and 12-16 pg/mL for PBMCs and macrophages, respectively. The levels of IL-6 were 0.11 g/mL and 0.019 pg/mL for PBMCs and macrophages, respectively. The results were not statistically significant in difference for IL-1β, IL-6, and IL-8 (p > 0.001) when N9 was compared to KY jelly. However, the results were significant when comparing N9 to KY jelly for TNF-α (p < 0.001) production. The two microbicides tested in their non-toxic formulation in the two models of PBMCs and macrophages showed relatively low levels of IL-1b, TNF-α and IL-6. This indicated safety and low toxicity of these microbicide in terms of cytokines release. On the other hand, IL-8 has shown relatively higher levels in all microbicide tested in their non-toxic formulation.