Scientific Publications by FDA Staff

J Biomed Mater Res A 2014 Feb;102(2):305-14

Different molecular weight hyaluronic acid effects on human macrophage interleukin 1beta production.

Baeva LF, Lyle DB, Rios M, Langone JJ, Lightfoote MM

This study examined the effect of HA molecular weight on immune response. HA with molecular weights ranging from the unitary disaccharide unit (400 Dalton) up to 1.7x106 Dalton and with very low endotoxin contamination level (less than 0.03 EU/mg) was used. Primary human monocyte/macrophage cultures were assayed for IL-1beta production under a variety of inflammatory conditions with or without HA. Under the highest inflammatory states, production of Interleukin 1 beta (IL-1beta) was suppressed in the presence of high molecular weight hyaluronan (HMW-HA) and in the presence of low molecular weight hyaluronan (LMW-HA) at mg/mL concentrations. There was variability in the sensitivity of the response to HA fragments with MW below 5000 Da at micromolar concentrations. There was variability in IL-1 beta cytokine productions from donor to donor in unstimulated human cell cultures. This study supplements our previous published study which investigated the immunogenic effect of HA molecular weights using murine cell line RAW264.6, rat splenocytes, and rat adherent differentiated primary macrophages. These data support the hypothesis that if the amount of endotoxin is reduced to an extremely low level, LMW-HA may not directly provoke normal tissue macrophage-mediated inflammatory reactions.