tranilast and Graft-vs-Host-Disease

Fibrosis and excessive extracellular matrix production are characteristic features of lacrimal gland chronic GVHD (cGVHD). Tranilast (n-[3,4-anthoranilic acid]), used for fibrotic skin disease, inhibits transforming growth factor-beta-induced matrix production. We conducted a non-randomized study comparing 8 patients (five men, three women; median age, 47 years) given topical tranilast with 10 patients (three men, seven women; median age, 37 years) receiving therapy with topical artificial tears, sodium hyaluronate and vitamin A for mild ocular cGVHD. The tranilast group instilled topical tranilast and artificial tears q.i.d., beginning the day of dry eye diagnosis. The ocular surface and tear dynamics of each patient were evaluated before hematopoietic stem cell transplant, at the onset of dry eye and after 3 months of treatment. At 3 months, the scores of the Rose Bengal test and Schirmer test with nasal stimulation had significantly improved in the tranilast group compared with that in the control group (P<0.05). Furthermore, although five control patients (50%) developed severe dry eye within the treatment period, only one tranilast-treated patient (12.5%) did; the rest still had mild dry eye (P<0.05). These results suggest the hypothesis that topical tranilast may effectively retard the progression of mild dry eye associated with cGVHD.

Topics: Adult; Anti-Allergic Agents; Chronic Disease; Dry Eye Syndromes; Female; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Ophthalmic Solutions; ortho-Aminobenzoates; Tears

Chronic graft-versus-host disease (cGVHD) is a marked complication of hematopoietic stem cell transplantation, and multiple organs can be affected by cGVHD-induced inflammation and fibrosis. In clinical settings, immunosuppressive agents have been the last resort to treat cGVHD. However, it has been only partially effective for cGVHD. Hence, efficacious treatment of cGVHD is eagerly awaited. Our previous work suggested that oxidative stress was elevated in cGVHD-disordered lacrimal glands and that epithelial-to-mesenchymal transition (EMT) was implicated in fibrosis caused by ocular cGVHD. In addition, our recent article demonstrated that thioredoxin interaction protein (TXNIP) and transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-

Topics: Animals; Bone Marrow Transplantation; Carrier Proteins; Disease Models, Animal; Epithelial-Mesenchymal Transition; Fibrosis; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Inflammation; Mice; NF-kappa B; ortho-Aminobenzoates; Thioredoxins

Topics: Animals; Cell Division; Chronic Disease; Coronary Disease; Cyclosporine; Graft vs Host Disease; Heart Transplantation; Male; ortho-Aminobenzoates; Platelet Aggregation Inhibitors; Postoperative Complications; Rats; Rats, Inbred ACI; Rats, Inbred Strains; Trachea; Transplantation, Heterotopic; Transplantation, Homologous