To investigate the effects of hyaluronidase PH20 processed recombinant human hyaluronic acid fragments (bioactive HA, B-HA) on lipopolysaccharide (LPS)-induced inflammatory response in human dendritic cells (DC) and macrophages.

DC cells and human acute monocytic leukemia cells (THP-1) were pretreated with different concentrations of B-HA in absence or unabsence of LPS for different times. The levels of inflammatory cytokines in culture medium were measured by ELISA and inflammatory cytokines mRNA of cultured cells was detected by real-time PCR.

Compared with LPS-only group, the expression of proinflammatory cytokines TNF-α and IL-8 were significantly inhibited by B-HA 20 mg/ml in THP-1 cells, while the expression of anti-inflammatory cytokine IL-10 was significantly elevated. The mRNA levels of TNF-α, IL-8 and IL-10 were 24.41±1.94, 35.76±4.19 and 4.99±0.07 in B-HA treated group, respectively, while the LPS-only group were 38.48±1.47, 62.7±1.93 and 2.27±0.16, with significant differences (t = 5.781, P = 0.0290; t = 5.695, P = 0.0300; t = 15.20, P = 0.0040). The TNF-α, IL-8 and IL-10 protein levels in culture medium were (1 609.00±75.66) pg/ml, (213.10±9.14) pg/ml and (496.30±41.92) pg/ml, while the LPS-only group were (3 018±102.8) pg/ml, ( 587.4±3.140) pg/ml and (243.3±20.23) pg/ml, with significant differences (t = 11.04, P = 0.0080; t = 38.74, P = 0.0007; t = 5.434, P = 0.0320). Unfortunately, no effect of B-HA was observed in human PBMC differentiated DC cells (all P > 0.05).

B-HA was effective on regulating inflammatory cytokines and could inhibit the inflammatory response in human macrophage. There was no significant effect on the inflammatory response in human PBMC-differentiated DC cells. The effect of B-HA on regulating inflammatory response is selective.