Hyaluronidase treatment is associated with increased cytokine levels and reduced peritoneal neutrophil accumulation during LPS-induced inflammation.

Background: Hyaluronidases are classically described as spreading factors that facilitate venom dissemination through extracellular matrix degradation, but their immunomodulatory roles remain poorly defined. In particular, comparative data between native scorpion venom hyaluronidase and commercial bovine hyaluronidase remain limited. This study investigated whether hyaluronidase treatment was associated with condition-dependent changes in inflammatory parameters. Methods: BALB/c mice were subjected to lipopolysaccharide (LPS)-induced peritoneal inflammation and treated with a native Results: Under non-LPS conditions, both TsHyal-1 and PH20 increased neutrophil recruitment and IL-6/IL-1β levels, accompanied by mild to moderate tissue alterations. In contrast, during LPS-induced peritoneal inflammation, both enzymes induced a non-canonical inflammatory profile in which IL-6/IL-1β levels were increased while neutrophil recruitment was reduced. TsHyal-1 exhibited a more pronounced immunomodulatory profile than bovine PH20. These differences were observed despite equivalent catalytic activity and nearly molar dosing and may reflect intrinsic biochemical or structural characteristics of the enzymes. Conclusion: Treatment with TsHyal-1 and bovine PH20 was associated with context-dependent changes in inflammatory parameters in this experimental model. These findings expand current knowledge of hyaluronidase biology and provide a basis for future studies investigating their role in inflammatory regulation under defined inflammatory contexts.