Administration of Panobinostat Is Associated with Increased IL-17A mRNA in the Intestinal Epithelium of HIV-1 Patients

• Published in: Mediators of Inflammation 2015-01, Vol.2015 (2015), p.97-107-008
• Main Authors: Randel Nyengaard, Jens, Agnholt, Jørgen, Denton, Paul W., Søgaard, Ole S., Tolstrup, Martin, Østergaard, Lars, Bendix, Mia, Brinkmann, Christel R., Vad-Nielsen, Johan, Dige, Anders, Bjerg Christensen, Ane, Rasmussen, Thomas A.
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - immunology; Adult; Biopsy; Clinical Study; Clinical trials; Councils; Drug dosages; Drug therapy; Endoscopy; Epithelium; FDA approval; Gene Expression Regulation; Genetic aspects; Health aspects; Histone Deacetylase Inhibitors - pharmacology; HIV patients; HIV-1; Hospitals; Humans; Hydroxamic Acids - pharmacology; Indoles - pharmacology; Infectious diseases; Inflammation; Inflammatory bowel disease; Interferon-gamma - biosynthesis; Interleukin-17 - genetics; Intestinal Mucosa - immunology; Intestines; Lymphocyte Activation; Lymphocytes; Messenger RNA; Mortality; Mucous membrane; Patients; RNA, Messenger - analysis; Small intestine; Studies; T-Lymphocytes - immunology
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2015/120605

Intestinal CD4+ T cell depletion is rapid and profound during early HIV-1 infection. This leads to a compromised mucosal barrier that prompts chronic systemic inflammation. The preferential loss of intestinal T helper 17 (Th17) cells in HIV-1 disease is a driver of the damage within the mucosal barrier and of disease progression. Thus, understanding the effects of new therapeutic strategies in the intestines has high priority. Histone deacetylase (HDAC) inhibitors (e.g., panobinostat) are actively under investigation as potential latency reversing agents in HIV eradication studies. These drugs have broad effects that go beyond reactivating virus, including modulation of immune pathways. We examined colonic biopsies from ART suppressed HIV-1 infected individuals (clinicaltrials.gov: NCT01680094) for the effects of panobinostat on intestinal T cell activation and on inflammatory cytokine production. We compared biopsy samples that were collected before and during oral panobinostat treatment and observed that panobinostat had a clear biological impact in this anatomical compartment. Specifically, we observed a decrease in CD69+ intestinal lamina propria T cell frequency and increased IL-17A mRNA expression in the intestinal epithelium. These results suggest that panobinostat therapy may influence the restoration of mucosal barrier function in these patients.