Lipopolysaccharide from Actinobacillus actinomycetemcomitans stimulates production of interleukin-1β, tumor necrosis factor-α, interleukin-6 and interleukin-1 receptor antagonist in human whole blood

Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) is supposed to be an important etiological agent in localized juvenile periodontitis (LJP). We have studied the effect of lipopolysaccharide (LPS) extracted from these periodontopathogenic bacteria on synthesis of the proinflammatory cytokines, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) in human whole blood. LPS from A. actinomycetemcomitans in concentrations greater than or equal to 1 ng/ml induced a significant production of all these proinflammatory cytokines, whereas LPS from Escherichia coli (E. coli), strain 026:B6 had to be added in concentrations greater than or equal to 1 mu g/ml to obtain a similar effect. Similarly, LPS from A. actinomycetemcomitans greater than or equal to 0.1 ng/ml resulted in production of IL-1ra, while LPS from E. coli 026:B6 had to be added at greater than or equal to 10 ng/ml to obtain similar effects. It has been suggested that the ratio between production of proinflammatory and anti-inflammatory cytokines may influence the outcome of periodontal diseases. Other in vitro and in vivo studies have, however, indicated that very large excesses (100-1000 times) of TL-1ra compared to IL-1 beta are required to shift the IL-1ra:IL-1 beta ratio in favor of an inhibition of IL-1 bioactivity. In our ex vivo system, we found that stimulation with extremely low doses of A. actinomycetemcomitans LPS (0.1-1 ng/ml) resulted in IL-1ra production solely, without concomitant production of IL-1 beta, the excess of IL-1ra over IL-1 beta peaking at 1 ng/ml, which accordingly should suggest that LPS from A. actinomycetemcomitans primarily has proinflammatory effects.