nifuroxazide and Graft-vs-Host-Disease

Graft‑vs.‑host disease (GvHD) is a major and lethal complication of allogeneic bone marrow transplantation (allo‑BMT). Although great development has been made, the treatment progress of this disorder is slow. Research has illustrated that STAT3 was critical for T cell alloactivation in GvHD. In the present study, the authors hypothesized that nifuroxazide, as the STAT3 inhibitor, treatment may attenuate the development of acute GvHD (aGvHD). The results demonstrated that nifuroxazide suppressed the development of aGvHD and significantly delayed aGvHD‑induced lethality. Mice receiving nifuroxazide had mostly normal‑appearing skin with minimal focal ulceration, mild edema and congestion in the liver, and a less‑pronounced villus injury and less inflammatory infiltrate in the small intestine. Treatment with nifuroxazide inhibited the activation of STAT3, resulting in the regulation of the CD4+ T cells and CD4+CD25+ T cells and reduction of interferon‑γ and tumor necrosis factor‑α levels. In conclusion, nifuroxazide may be efficacious for post‑transplant of GvHD, providing a potent drug for use as a prophylactic or as a second‑line therapy for aGvHD in clinical trials.

Topics: Animals; Bone Marrow Transplantation; CD4-Positive T-Lymphocytes; Gene Expression Regulation; Graft vs Host Disease; Humans; Hydroxybenzoates; Interferon-gamma; Lymphocyte Activation; Mice; Nitrofurans; STAT3 Transcription Factor; Transplantation, Homologous; Tumor Necrosis Factor-alpha

Acute graft-versus-host disease (aGvHD) is the major barrier to the broader use of allogenetic hematopoietic stem cells. However, currently these are no highly specific and efficient drugs. Monotherapy is not sufficient and more efficient and safe therapeutic regimen are urgent need. Studies demonstrated TLR9 and Stat3 signal pathways are critical for antigen-presenting cell maturation and T-cell activation, which are important mediators in aGvHD. Specific block these two critical signal pathways using their inhibitors SAT05f and nifuroxazide may be the novel strategies for aGvHD therapy. The results showed combined therapy significantly decreased the severity of aGvHD and prolonged the survival rate. Furthermore, after treatment, the activation of CD4

Topics: Animals; Bone Marrow Transplantation; Cell Differentiation; Cytokines; Drug Therapy, Combination; Graft vs Host Disease; Hydroxybenzoates; Lymphocyte Activation; Lymphocyte Count; Mice, Inbred BALB C; Mice, Inbred C57BL; Models, Biological; Nitrofurans; Oligodeoxyribonucleotides; Organ Specificity; Severity of Illness Index; STAT3 Transcription Factor; Survival Analysis; T-Lymphocytes, Regulatory; Toll-Like Receptor 9; Transplantation, Homologous