Modulation of Pro- and Anti-Inflammatory Cytokines by Melaleuca cajuputi subsp. cajuputi Powell Ethanolic Leaf Extract (MC-ELE) in BALB/c Mice

Background: Cytokine storm-like inflammation includes an imbalanced immune response, where excessive interleukin-6 (IL-6) and inadequate IL-10 play a central role in increasing tissue injury. Melaleuca cajuputi leaves are known to contain anti-inflammatory bioactive compounds. However, the potential to modulate the dysregulated cytokine response remains underexplored. Objective: This study aimed to evaluate the immunomodulatory effects of Melaleuca cajuputi subsp. cajuputi Powell Ethanolic Leaf Extract (MC-ELE) on IL-6, IL-6R, and IL-10 levels in a BALB/c mouse model of lung inflammation induced by lipopolysaccharide (LPS). Methods: Phytochemical screening was performed to identify active constituents in MC-ELE. Male BALB/c mice were intratracheally challenged with LPS (mg·kg−1 BW) to induce cytokine storm-like inflammation. After 24 h, mice received oral MC-ELE at doses of 750, 1500, 3000 mg·kg−1 BW, or dexamethasone (10 mg·kg−1 BW), for seven consecutive days. On day eight, serum and bronchoalveolar lavage fluid (BALF) were collected for IL-6, IL-6R, and IL-10 assessment using ELISA. Furthermore, body weight changes and clinical symptoms were monitored throughout the study. Results: MC-ELE was confirmed to contain anti-inflammatory compounds. Across all groups, IL-6 concentrations in BALF were consistently higher than in serum, with the LPS-only group showing the greatest elevation. Serum IL-6R levels exceeded BALF IL-6R levels in most groups, except at 1500 mg·kg−1 BW MC-ELE dose. BALF IL-10 was higher compared with serum in all MC-ELE-treated groups. Therefore, MC-ELE might preferentially enhance anti-inflammatory responses within the pulmonary microenvironment. There was no observed toxicity or weight loss at doses up to 3000 mg·kg−1 BW. Conclusions: MC-ELE reported promising immunomodulatory activity by lowering IL-6 and IL-6R levels while enhancing IL-10 responses in lung inflammation induced by LPS within lung tissue. These results suggested its potential as a natural therapeutic candidate for managing severe inflammatory conditions.