# Microneurotrophin BNN27 Exerts Significant Anti-Inflammatory Effects on Murine T-Lymphocytes Following CFA-Induced Inflammatory Pain

**Authors:** Smaragda Poulaki, Aikaterini Kalantidou, Ioanna Lapi, Achille Gravanis, Maria Venihaki

PMC · DOI: 10.3390/ijms26125498 · International Journal of Molecular Sciences · 2025-06-08

## TL;DR

BNN27, a synthetic microneurotrophin, reduces inflammation and pain by boosting T-cell activity and altering key inflammatory and opioid-related molecules in mice.

## Contribution

BNN27's novel anti-inflammatory and analgesic effects on T-lymphocytes during CFA-induced inflammation are demonstrated.

## Key findings

- BNN27 significantly increased T-lymphocyte proliferation.
- BNN27 reduced IL-6 and TNF-α protein levels.
- BNN27 increased mRNA expression of μ-opioid receptor and opioid peptides PENK and POMC.

## Abstract

During tissue injury or infection, leukocytes are activated to produce proinflammatory mediators, which trigger the immune system to produce anti-inflammatory and analgesic molecules. Our previous studies provide evidence that synthetic microneurotrophins, like BNN27, exert significant analgesic and anti-inflammatory effects during Complete Freund’s Adjuvant (CFA)-induced inflammation and pain. Thus, the aim of the present study was to examine if the effect of BNN27 on inflammatory pain is mediated at least in part by activation of T-lymphocytes. For this purpose, six hours following the injection of CFA, spleens were harvested in PBS and lymphocytes were collected and placed in medium containing concanavalin-A and IL-2 to prompt T-lymphocyte proliferation and differentiation. Cells were then treated with BNN27 at different concentrations and the media and cells were collected for ELISA and PCR assays. The proliferation rate of T-cells was also examined using the MTT assay. Our results showed that BNN27 significantly increased the proliferation of T-lymphocytes. In addition, BNN27 significantly decreased IL-6 and TNF-α protein levels, while it increased the mRNA expression of μ-opioid receptor and opioid peptides PENK and POMC at different time points. Our data demonstrate considerable anti-inflammatory and analgesic effects of BNN27, making it a promising molecule for inflammation and pain management.

## Linked entities

- **Genes:** PENK (proenkephalin) [NCBI Gene 5179], POMC (proopiomelanocortin) [NCBI Gene 5443]
- **Proteins:** IL6 (interleukin 6), TNF (tumor necrosis factor)
- **Chemicals:** BNN27 (PubChem CID 44542345), concanavalin-A (PubChem CID 155486958), IL-2 (PubChem CID 51397006)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Pomc (pro-opiomelanocortin-alpha) [NCBI Gene 18976] {aka ACTH, BE, Beta-LPH, Clip, Gamma-LPH, Npp}
- **Diseases:** Inflammatory (MESH:D007249), infection (MESH:D007239), tissue injury (MESH:D017695), Pain (MESH:D010146)
- **Chemicals:** PBS (MESH:D007854), MTT (MESH:C070243), BNN27 (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12193358/full.md

## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC12193358/full.md

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Source: https://tomesphere.com/paper/PMC12193358