PMID- 28254742
OWN - NLM
STAT- MEDLINE
DCOM- 20170901
LR  - 20210202
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 129
IP  - 18
DP  - 2017 May 4
TI  - Pirfenidone ameliorates murine chronic GVHD through inhibition of macrophage 
      infiltration and TGF-beta production.
PG  - 2570-2580
LID - 10.1182/blood-2017-01-758854 [doi]
AB  - Allogeneic hematopoietic stem cell transplantation is hampered by chronic 
      graft-versus-host disease (cGVHD), resulting in multiorgan fibrosis and 
      diminished function. Fibrosis in lung and skin leads to progressive bronchiolitis 
      obliterans (BO) and scleroderma, respectively, for which new treatments are 
      needed. We evaluated pirfenidone, a Food and Drug Administration (FDA)-approved 
      drug for idiopathic pulmonary fibrosis, for its therapeutic effect in cGVHD mouse 
      models with distinct pathophysiology. In a full major histocompatibility complex 
      (MHC)-mismatched, multiorgan system model with BO, donor T-cell responses that 
      support pathogenic antibody production are required for cGVHD development. 
      Pirfenidone treatment beginning one month post-transplant restored pulmonary 
      function and reversed lung fibrosis, which was associated with reduced macrophage 
      infiltration and transforming growth factor-beta production. Pirfenidone dampened 
      splenic germinal center B-cell and T-follicular helper cell frequencies that 
      collaborate to produce antibody. In both a minor histocompatibility 
      antigen-mismatched as well as a MHC-haploidentical model of sclerodermatous 
      cGVHD, pirfenidone significantly reduced macrophages in the skin, although 
      clinical improvement of scleroderma was only seen in one model. In vitro 
      chemotaxis assays demonstrated that pirfenidone impaired macrophage migration to 
      monocyte chemoattractant protein-1 (MCP-1) as well as IL-17A, which has been 
      linked to cGVHD generation. Taken together, our data suggest that pirfenidone is 
      a potential therapeutic agent to ameliorate fibrosis in cGVHD.
CI  - (c) 2017 by The American Society of Hematology.
FAU - Du, Jing
AU  - Du J
AD  - Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic 
      Cancer Center, University of Minnesota, Minneapolis, MN.
FAU - Paz, Katelyn
AU  - Paz K
AD  - Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic 
      Cancer Center, University of Minnesota, Minneapolis, MN.
FAU - Flynn, Ryan
AU  - Flynn R
AD  - Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic 
      Cancer Center, University of Minnesota, Minneapolis, MN.
FAU - Vulic, Ante
AU  - Vulic A
AD  - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns 
      Hopkins University, Baltimore, MD.
FAU - Robinson, Tara M
AU  - Robinson TM
AD  - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns 
      Hopkins University, Baltimore, MD.
FAU - Lineburg, Katie E
AU  - Lineburg KE
AD  - QIMR Berghofer Medical Research Institute, Brisbane, Australia.
FAU - Alexander, Kylie A
AU  - Alexander KA
AD  - QIMR Berghofer Medical Research Institute, Brisbane, Australia.
FAU - Meng, Jingjing
AU  - Meng J
AD  - Division of Surgical Oncology, Department of Surgery, Sylvester Comprehensive 
      Cancer Center, University of Miami, Miami, FL.
FAU - Roy, Sabita
AU  - Roy S
AD  - Division of Surgical Oncology, Department of Surgery, Sylvester Comprehensive 
      Cancer Center, University of Miami, Miami, FL.
FAU - Panoskaltsis-Mortari, Angela
AU  - Panoskaltsis-Mortari A
AD  - Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic 
      Cancer Center, University of Minnesota, Minneapolis, MN.
FAU - Loschi, Michael
AU  - Loschi M
AD  - Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic 
      Cancer Center, University of Minnesota, Minneapolis, MN.
FAU - Hill, Geoffrey R
AU  - Hill GR
AD  - QIMR Berghofer Medical Research Institute, Brisbane, Australia.
FAU - Serody, Jonathan S
AU  - Serody JS
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel 
      Hill, NC.
FAU - Maillard, Ivan
AU  - Maillard I
AD  - Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, 
      Ann Arbor, MI.
FAU - Miklos, David
AU  - Miklos D
AD  - Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA.
FAU - Koreth, John
AU  - Koreth J
AD  - Dana-Farber Cancer Institute, Boston, MA; and.
FAU - Cutler, Corey S
AU  - Cutler CS
AD  - Dana-Farber Cancer Institute, Boston, MA; and.
FAU - Antin, Joseph H
AU  - Antin JH
AD  - Dana-Farber Cancer Institute, Boston, MA; and.
FAU - Ritz, Jerome
AU  - Ritz J
AD  - Dana-Farber Cancer Institute, Boston, MA; and.
FAU - MacDonald, Kelli P
AU  - MacDonald KP
AD  - QIMR Berghofer Medical Research Institute, Brisbane, Australia.
FAU - Schacker, Timothy W
AU  - Schacker TW
AD  - Department of Medicine, University of Minnesota, Minneapolis, MN.
FAU - Luznik, Leo
AU  - Luznik L
AD  - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns 
      Hopkins University, Baltimore, MD.
FAU - Blazar, Bruce R
AU  - Blazar BR
AD  - Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic 
      Cancer Center, University of Minnesota, Minneapolis, MN.
LA  - eng
GR  - P01 AI056299/AI/NIAID NIH HHS/United States
GR  - T32 AI007313/AI/NIAID NIH HHS/United States
GR  - R01 CA122779/CA/NCI NIH HHS/United States
GR  - R01 AI091627/AI/NIAID NIH HHS/United States
GR  - R01 HL126530/HL/NHLBI NIH HHS/United States
GR  - P30 CA016086/CA/NCI NIH HHS/United States
GR  - T32 CA009138/CA/NCI NIH HHS/United States
GR  - K08 HL107756/HL/NHLBI NIH HHS/United States
GR  - P01 CA047741/CA/NCI NIH HHS/United States
GR  - R01 AI093319/AI/NIAID NIH HHS/United States
GR  - P01 CA142106/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170302
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Il17a protein, mouse)
RN  - 0 (Interleukin-17)
RN  - 0 (Pyridones)
RN  - 0 (Transforming Growth Factor beta)
RN  - D7NLD2JX7U (pirfenidone)
SB  - IM
CIN - Blood. 2017 May 4;129(18):2463-2464. PMID: 28473413
MH  - Allografts
MH  - Animals
MH  - B-Lymphocytes/immunology/pathology
MH  - Bronchiolitis Obliterans/genetics/immunology/pathology/prevention & control
MH  - Chemokine CCL2/genetics/immunology
MH  - Disease Models, Animal
MH  - Graft vs Host Disease/genetics/immunology/pathology/*prevention & control
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Interleukin-17/genetics/immunology
MH  - Macrophages/*immunology/pathology
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Pulmonary Fibrosis/genetics/immunology/pathology/prevention & control
MH  - Pyridones/*pharmacology
MH  - Skin Diseases/genetics/immunology/pathology/*prevention & control
MH  - T-Lymphocytes, Helper-Inducer/immunology/pathology
MH  - Transforming Growth Factor beta/genetics/*immunology
PMC - PMC5418639
EDAT- 2017/03/04 06:00
MHDA- 2017/09/02 06:00
PMCR- 2018/05/04
CRDT- 2017/03/04 06:00
PHST- 2017/01/06 00:00 [received]
PHST- 2017/02/23 00:00 [accepted]
PHST- 2017/03/04 06:00 [pubmed]
PHST- 2017/09/02 06:00 [medline]
PHST- 2017/03/04 06:00 [entrez]
PHST- 2018/05/04 00:00 [pmc-release]
AID - S0006-4971(20)33422-4 [pii]
AID - 2017/758854 [pii]
AID - 10.1182/blood-2017-01-758854 [doi]
PST - ppublish
SO  - Blood. 2017 May 4;129(18):2570-2580. doi: 10.1182/blood-2017-01-758854. Epub 2017 
      Mar 2.