Oral intake of phenylbutyrate with or without vitamin D3 upregulates the cathelicidin LL-37 in human macrophages: a dose finding study for treatment of tuberculosis.
Mily. Akhirunnesa A; Rekha. Rokeya Sultana RS; Kamal. S M Mostafa SM; Akhtar. Evana E; Sarker. Protim P; Rahim. Zeaur Z; Gudmundsson. Gudmundur H GH; Agerberth. Birgitta B; Raqib. Rubhana R
Key Findings
- 500 mg phenylbutyrate twice daily plus 5,000 IU vitamin D3 daily gave the strongest increase in LL‑37 peptide and its mRNA in macrophages and lymphocytes
- This dosing regimen also significantly improved the ability of macrophages to kill Mycobacterium tuberculosis in vitro
- Lower (250 mg) or higher (1,000 mg) phenylbutyrate doses, and vitamin D3 alone, were less effective at raising LL‑37 or enhancing bacterial killing
Practical Outcomes
- For biohackers interested in immune support, the study points to a specific supplement protocol—500 mg phenylbutyrate twice daily with 5,000 IU vitamin D3 daily—as a way to boost LL‑37 production and potentially enhance antimicrobial defenses. Users should monitor vitamin D status and consider that the evidence is from short‑term lab studies, not clinical proof of disease treatment.
Summary
Taking 500 mg of phenylbutyrate twice a day together with 5,000 IU of vitamin D3 each day raises the body’s antimicrobial peptide LL‑37 in immune cells and makes macrophages better at killing TB bacteria in lab tests, suggesting this combo could be used to boost innate immunity.
Abstract
We earlier showed that 4-phenylbutyrate (PB) can induce cathelicidin LL-37 expression synergistically with 1,25-dihydroxyvitamin D3 in a lung epithelial cell line. We aimed to evaluate a therapeutic dose of PB alone or in combination with vitamin D3 for induction of LL-37 expression in immune cells and enhancement of antimycobacterial activity in monocyte-derived macrophages (MDM). Healthy volunteers were enrolled in an 8-days open trial with three doses of PB [250 mg (Group-I), 500 mg (Group-II) or 1000 mg (Group-III)] twice daily (b.d.) together with vitamin D3 {5000 IU once daily (o.d.)}, PB (500 mg b.d.) (Group-IV) or vitamin D3 (5000 IU o.d.) (Group-V), given orally for 4 days. Blood was collected on day-0, day-4 and day-8; plasma was separated, peripheral blood mononuclear cells (PBMC), non-adherent lymphocytes (NAL) and MDM were cultured. LL-37 transcript in cells and peptide concentrations in supernatant were determined by qPCR and ELISA, respectively. In plasma, 25-hydorxyvitamin D3 levels were determined by ELISA. MDM-mediated killing of Mycobacterium tuberculosis (Mtb) (H37Rv) was performed by conventional culture method. MDM from Group-II had increased concentration of LL-37 peptide and transcript at day-4, while Group-I showed increased transcript at day-4 and day-8 compared to day-0 (p < 0.05). Both Group-I and -II exhibited higher levels of transcript on day-4 compared to Group-III and Group-V (p < 0.035). Increased induction of peptide was observed in lymphocytes from Group-II on day-4 compared to Group-I and Group-IV (p < 0.05), while Group-IV showed increased levels on day-8 compared to Group-I and Group-III (p < 0.04). Intracellular killing of Mtb on day-4 was significantly increased compared to day-0 in Group-I, -II and -V (p < 0.05). The results demonstrate that 500 mg b.d. PB with 5000 IU o.d. vitamin D3 is the optimal dose for the induction of LL-37 in macrophages and lymphocytes and intracellular killing of Mtb by macrophages. Hence, this dose has potential application in the treatment of TB and is now being used in a clinical trial of adults with active pulmonary TB (NCT01580007).
Study Information
pubmed
2013
2013-04-16T00:00:00.000Z
10.1186/1471-2466-13-23
88
43