Combined cell wall polysaccharide, mycotoxin and bacterial lipopolysaccharide exposure and inflammatory cytokine responses.

Human exposure to environmental microbes occurs regularly. Microbial compounds may interact with each other to affect cellular responses. We hypothesized that interactions between microbial compounds could modulate inflammatory cytokine responses in vitro. We investigated monocyte production of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) and the regulatory cytokine interleukin-10 (IL-10) after combined exposure to the fungal cell wall polysaccharide mannan and to the beta-glucan laminarin, the mycotoxin citrinin and bacterial lipopolysaccharide (LPS). Interactions between the cell wall microbial compounds were estimated statistically in a general linear mixed model. We found that LPS (100 ng/ml) and the used beta-glucan (up to 1000 microg/ml) significantly interacted with each other to reduce TNF-alpha production. Mannan (up to 100 microg/ml) did not interact with the beta-glucan, but interacted with LPS. IL-10 production was induced by LPS only. The mycotoxin citrinin did not induce cytokine production, but was toxic to the cells in a dose- and time-dependent manner. However, non-toxic doses of citrinin reduced LPS-induced IL-10 production while LPS-induced TNF-alpha production was not similarly reduced by citrinin. In conclusion, interactions between microbial compounds can modulate cellular inflammatory cytokine production and experimental investigations of one compound at a time could give misleading conclusions about these combined effects.