PMID- 25540922 OWN - NLM STAT- MEDLINE DCOM- 20151201 LR - 20171116 IS - 1879-0542 (Electronic) IS - 0165-2478 (Linking) VI - 163 IP - 2 DP - 2015 Feb TI - Innate immunity alterations in idiopathic interstitial pneumonias and rheumatoid arthritis-associated interstitial lung diseases. PG - 179-86 LID - S0165-2478(14)00307-1 [pii] LID - 10.1016/j.imlet.2014.12.004 [doi] AB - BACKGROUND: This is a prospective cohort study elucidating innate immunity in idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), rheumatoid arthritis-associated usual interstitial pneumonia (RA-UIP) and RA-associated non specific interstitial pneumonia (RA-NSIP). METHODS: 23 IPF subjects, 9 COP subjects, 5 RA-UIP subjects, 8 RA-NSIP subjects were enrolled. 10 subjects were excluded. 19 healthy subjects served as controls. Blood and bronchoalveolar lavage (BAL) were obtained. Natural killer (NK) and NKT cells, NK cells apoptosis and the expression of triggering receptor expressed on myeloid cells type 1 (TREM-1) were assessed. Tumor necrosis factor-alpha (TNF-alpha) production was measured in cell cultures after stimulation with lipopolysaccharide endotoxin (LPS) and Pam3CysSK3, and in BAL. Surface expression of Toll-like receptors (TLR) 2 and 4 on peripheral blood monocytes (PBMC's) and circulating NK cells was also assessed. RESULTS: RA-NSIP had low blood NKs, marginally insignificant (p=0.07). These NKs poorly produced TNF-alpha after LPS stimulation. TLR's expression on NK cells was similar throughout disease groups and controls. PBMC's mainly from IPF patients exhibited low TNF-alpha production after LPS stimulation but not after Pam3CysSK3 stimulation, while TLR4 expression on PBMC's was found normal in all study groups. TLR2 expression on PBMC's was increased in IPF, but mainly in COP, RA-UIP and RA-NSIP (p=0.015). TREM-1 expression was significant on COP monocytes and on COP neutrophils versus controls. RA-NSIP monocytes also exhibited TREM-1 expression (p=0.07). Decreased TNF-alpha concentration in BAL was finally observed in IPF and RA-UIP. CONCLUSIONS: Innate immunity in the lungs and the peripheral circulation in IPF and RA-UIP are similar and more fibrotic than in RA-NSIP which is characterized by NK cell depletion and dysfunction. TREM-1 and TLR's likely affect patterns of inflammation in various interstitial lung diseases. CI - Copyright (c) 2014 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved. FAU - Papanikolaou, Ilias C AU - Papanikolaou IC AD - 3rd Pulmonary Department, Sismanoglion General Hospital, Sismanogliou 1, 15126 Attica, Greece. Electronic address: ipapanikolaou76@hotmail.com. FAU - Boki, Kyriaki A AU - Boki KA AD - Rheumatology Department, Sismanoglion General Hospital, Sismanogliou 1, 15126 Attica, Greece. Electronic address: kboki@otenet.gr. FAU - Giamarellos-Bourboulis, Evangelos J AU - Giamarellos-Bourboulis EJ AD - 4th Department of Internal Medicine, ATTIKON University General Hospital, Rimini 1, 12462 Attica, Greece. Electronic address: egiamarel@med.uoa.gr. FAU - Kotsaki, Antigoni AU - Kotsaki A AD - 4th Department of Internal Medicine, ATTIKON University General Hospital, Rimini 1, 12462 Attica, Greece. Electronic address: antigonebut@yahoo.com. FAU - Kagouridis, Konstantinos AU - Kagouridis K AD - 3rd Pulmonary Department, Sismanoglion General Hospital, Sismanogliou 1, 15126 Attica, Greece. Electronic address: konstantinos.kagouridis@gmail.com. FAU - Karagiannidis, Napoleon AU - Karagiannidis N AD - 3rd Pulmonary Department, Sismanoglion General Hospital, Sismanogliou 1, 15126 Attica, Greece. Electronic address: nap@karagianidis.gr. FAU - Polychronopoulos, Vlasis S AU - Polychronopoulos VS AD - 3rd Pulmonary Department, Sismanoglion General Hospital, Sismanogliou 1, 15126 Attica, Greece. Electronic address: vlasispo@hotmail.com. LA - eng PT - Journal Article DEP - 20141223 PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, Immunologic) RN - 0 (TREM1 protein, human) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 0 (Triggering Receptor Expressed on Myeloid Cells-1) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adult MH - Aged MH - Arthritis, Rheumatoid/*immunology/metabolism MH - Bronchoalveolar Lavage Fluid/chemistry/cytology/immunology MH - Cells, Cultured MH - Female MH - Flow Cytometry MH - Humans MH - Idiopathic Interstitial Pneumonias/*immunology/metabolism MH - Immunity, Innate/*immunology MH - Killer Cells, Natural/immunology/metabolism MH - Leukocytes, Mononuclear/immunology/metabolism MH - Lung/immunology/metabolism/pathology MH - Lung Diseases, Interstitial/*immunology/metabolism MH - Male MH - Membrane Glycoproteins/immunology/metabolism MH - Middle Aged MH - Natural Killer T-Cells/immunology/metabolism MH - Prospective Studies MH - Pulmonary Fibrosis/immunology/metabolism MH - Receptors, Immunologic/immunology/metabolism MH - Toll-Like Receptor 2/immunology/metabolism MH - Toll-Like Receptor 4/immunology/metabolism MH - Triggering Receptor Expressed on Myeloid Cells-1 MH - Tumor Necrosis Factor-alpha/immunology/metabolism OTO - NOTNLM OT - Innate immunity OT - Interstitial lung diseases OT - Natural killer cells OT - Rheumatoid arthritis OT - Toll-like receptors OT - Triggering receptor expressed on myeloid cells 1 EDAT- 2014/12/30 06:00 MHDA- 2015/12/15 06:00 CRDT- 2014/12/27 06:00 PHST- 2014/06/15 00:00 [received] PHST- 2014/12/01 00:00 [revised] PHST- 2014/12/03 00:00 [accepted] PHST- 2014/12/27 06:00 [entrez] PHST- 2014/12/30 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - S0165-2478(14)00307-1 [pii] AID - 10.1016/j.imlet.2014.12.004 [doi] PST - ppublish SO - Immunol Lett. 2015 Feb;163(2):179-86. doi: 10.1016/j.imlet.2014.12.004. Epub 2014 Dec 23.