# A Human β-Defensin-Based Recombinant Protein DF2-HSA Ameliorates Cytokine Storm

## TL;DR

A new recombinant protein DF2-HSA reduces cytokine storms and tissue damage in a mouse model.

## Contribution

DF2-HSA, a fusion of HBD-2 and albumin, is shown to reduce inflammation and tissue injury in cytokine storm models.

## Key findings

- DF2-HSA reduced mortality and prolonged HBD-2 retention in cytokine storm mice.
- DF2-HSA decreased inflammatory cytokines, vascular leakage, and lung injury.
- DF2-HSA alleviated lung and small intestine damage in the mouse model.

## Abstract

Cytokine storm is a critical driver of acute respiratory distress syndrome and multiple organ failure. Human β-defensin 2 (HBD-2) is the first inducible defensin discovered in human body. Defensin can resist pathogenic microorganisms invading the body through direct bactericidal effect and also modulates acquired immune response. Albumin exhibits immunomodulatory properties and can reduce the level of inflammatory cytokines to improve the systemic inflammatory response. We previously engineered a recombinant fusion protein, DF2-HSA, comprising two HBD-2 molecules linked to human serum albumin. Here, we evaluated its effect on cytokine storm using a lipopolysaccharide (LPS)-induced cytokine storm murine model (BALB/c athymic mice, female). DF2-HSA reduced the mortality in cytokine storm murine model and prolonged the retention time of HBD-2 in the body. A Luminex assay showed that DF2-HSA reduced the production of multiple inflammatory cytokines in cytokine storm murine model. Evans blue staining showed that DF2-HSA reduced vascular leakage. Transmission electron microscopy showed that DF2-HSA reduced the lung injury of cytokine storm mice. The pathological results showed that DF2-HSA alleviated the lung and small intestine damage of cytokine storm mice. In summary, DF2-HSA effectively inhibits cytokine storms and ameliorates associated tissue damage.