# Sea cucumber protein hydrolysate restores the Th1/Th2 paradigm in cyclophosphamide-induced immunosuppressed mice

## TL;DR

A protein hydrolysate from sea cucumbers helps restore immune balance in mice treated with an immunosuppressive drug.

## Contribution

The study demonstrates that sea cucumber protein hydrolysate can rebalance Th1/Th2 immune responses in immunosuppressed mice.

## Key findings

- SCPH reversed CYP-induced immune suppression by restoring immune organ indices and normalizing immune cell levels.
- SCPH upregulated Th1 genes (IFNG, TBX21) and downregulated Th2 genes (IL4, GATA3) in immunosuppressed mice.
- Histological analysis showed improved spleen architecture and altered T-bet/GATA3 expression following SCPH treatment.

## Abstract

Immunocompetence reflects the immune system’s capacity to mount effective responses against antigens. Cyclophosphamide (CYP), a chemotherapeutic and experimental immunosuppressive agent, disrupts T-helper (Th)1/Th2 balance and compromises immune organ integrity. Bioactive peptides derived from the sea cucumber Apostichopus japonicus, which is rich in type I collagen, have shown emerging immunomodulatory potential.

A collagenase-derived sea cucumber protein hydrolysate (SCPH) was prepared using Clostridium collagenase-I and characterized for amino acid composition and peptide profiles. BALB/c mice were administered CYP (80 mg/kg, i.p.) to induce immunosuppression, followed by oral SCPH treatment. Body weight, spleen and thymus indices, leukocyte counts, Th1/Th2-associated gene expression (IFNG, TBX21, IL4, GATA3), serum cytokines and immunoglobulins, and splenic histology and immunohistochemistry were evaluated.

CYP treatment induced body weight loss, reduced immune organ indices, altered leukocyte profiles, and disrupted Th1/Th2-associated markers. SCPH administration partially reversed these changes by restoring spleen and thymus indices, normalizing circulating immune cell levels, upregulating Th1-associated genes (IFNG, TBX21), and downregulating Th2-associated genes (IL4, GATA3). SCPH also increased serum Th1 mediators (IFNG, IgG, IgM) while reducing Th2-associated markers (IL-4, IL-10, IgA, sIgA). Histological and immunohistochemical analyses confirmed improved splenic architecture with elevated T-bet and reduced GATA3 expression.

These findings indicate that SCPH promotes Th1-biased immune rebalancing in CYP-induced immunosuppressed mice, suggesting its potential as a marine-derived immunonutritional agent. Further mechanistic studies are warranted to explore its therapeutic and translational applications.