Effect of ACTH4-10Pro8-Gly9-Pro10 on anti-inflammatory cytokine (IL-4, IL-10, IL-13) expression in acute spinal cord injury models (male Sprague Dawley rats).
Asadullah. Asadullah A; Bajamal. Abdul Hafid AH; Parenrengi. Muhammad Arifin MA; Turchan. Agus A; Utomo. Budi B; Sudiana. I Ketut IK; Subagio. Eko Agus EA
Key Findings
- Intranasal semax increased anti‑inflammatory cytokines (IL‑4, IL‑10, IL‑13) in the spinal cord of rats after injury.
- The increase was most pronounced at 3 hours post‑injury for mild injuries and at 6 hours for severe injuries.
- The study did not determine the optimal dose or whether these effects translate to functional recovery or to humans.
Practical Outcomes
- For biohackers, this research suggests semax has anti‑inflammatory potential, but it’s an early‑stage animal study. There’s no clear dosing guidance or evidence of benefit for healthy people, so it’s not ready for practical use in longevity or performance protocols. More human‑focused research is needed before considering it for self‑experimentation.
Summary
In rats with a spinal cord injury, giving the peptide semax through the nose boosted levels of anti‑inflammatory proteins (IL‑4, IL‑10, IL‑13) compared to a salt solution. The effect was strongest a few hours after the injury and varied with injury severity. This shows semax can modulate inflammation in an acute injury model, but the study was done in animals, not people.
Abstract
Spinal cord injury (SCI) is a damage to the spinal cord caused mainly by trauma resulting in major motor, sensory and autonomic dysfunctions. Its final neurological outcome is determined by both primary and secondary injury processes. A key component of secondary injury mechanisms after initial trauma is neuroinflammation. A neuroprotective compound, ACTH <sub>4-10</sub>Pro <sup>8</sup>-Gly <sup>9</sup>-Pro <sup>10</sup> (ACTH <sub>4-10</sub>) also known as semax, has shown neuroprotective and anti-inflammatory properties. ACTH <sub>4-10</sub> has also been actively used in the treatment of brain ischemia without serious complication reported. Here, we analyzed the effects of ACTH <sub>4-10</sub> at regulating the inflammatory cascade in SCI by looking at anti-inflammatory cytokine (IL-4, IL-10 and IL-13) levels after acute SCI. We carried out laminectomies in male Sprague Dawley rats at the second thoracic vertebrae. After laminectomy, we exposed the myelum and created mild SCI models with 20-g, and severe SCI with 35-g aneurysm clips. ACTH <sub>4-10</sub> was administered intranasally to the treatment group and 0.9% NaCl to the control group (placebo). Both groups were kept alive and terminated at 3 and 6 hours. The tissue sample preparations were fixed in formalin and examined for immunohistochemistry. Quantitative measurement of the cytokines was done in the posterior horn area with specific associated anti-monoclonal antibodies. Rats with mild SCI that were given ACTH <sub>4-10</sub> showed greater anti-inflammatory levels at 3 hours post-compression but only IL-10 and IL-13 were elevated significantly at 6 hours. Rats with severe compression in ACTH <sub>4-10</sub> group showed greater levels of IL-10, IL-13 at 3 hours and IL-4, IL-10 at 6 hours compared with the placebo group. Administration of ACTH <sub>4-10</sub>Pro <sup>8</sup>-Gly <sup>9</sup>-Pro <sup>10</sup> intranasal can increase anti-inflammatory cytokine expression in Sprague Dawley rat models with mild and severe SCI. Expression of anti-inflammatory cytokines was greater in mild compression and 3-hour termination. Further research is needed to determine the optimal dose and clinical outcome <i>in vivo.</i>
Study Information
pubmed
2025
2025-09-22T00:00:00.000Z
10.12688/f1000research.127413.2
1
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