PRO-INFLAMMATORY ACTIVITY OF CONTAMINATING DNA IN HYALURONAN PREPARATIONS

Abstract

Hyaluronan (HA) preparations are currently used in the treatment of inflammatory disorders. Low molecular mass HA fragments are however believed to induce inflammation. In this study we have evaluated whether low molecular mass fragments derived from HA preparations induce the synthesis of the pro-inflammatory cytokines IL-12 and TNF-α by human monocytic cells. Since DNA from numerous species has been shown to possess pro-inflammatory activity, we have additionally tested for the presence of DNA in these preparations. We have found that low molecular mass fragments obtained from non-inflammatory HA preparation by sonication (3 × 105 Da) or by hyaluronidase digestion (1 × 104 Da) do not have the ability to induce IL-12 and TNF-α by human monocytic cells. We unexpectedly found however that high molecular mass HA present in 2 out of 7 HA preparations tested was able to stimulate the synthesis of significant levels of IL-12 and TNF-α. The pro-inflammatory cytokine-inducing activity was shown to be due to the presence of DNA, since treatment of the HA preparations with DNase I abrogated or significantly reduced the induction of cytokines. The presence of pro-inflammatory DNA in HA preparations should be evaluated before their use, not only for the treatment of patients with inflammatory disorders, but also before studying inflammatory processes.