TH1/TH2 immune response in lung fibroblasts in interstitial lung disease.
BACKGROUND
Inflammatory response in pulmonary fibrosis closely resembles a T-helper (Th) 2 immune response. For recruitment to an inflammatory lesion, the majority of Th1 cells express CXC chemokine receptor 3, recognizing monokine induced by interferon-gamma (Mig), interferon gamma-inducible protein of 10 kD (IP-10), and interferon-inducible T-cell alpha chemoattractant (I-TAC). Th2 cells express CC chemokine receptor 4, recognizing thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). We investigated the Th1/Th2 chemokine production patterns by lung fibroblasts and their evaluation in bronchoalveolar lavage (BAL) fluid of interstitial lung disease.


METHODS
The production pattern of Th1/Th2 chemokines by lung fibroblasts was examined in ELISA and quantitative reverse transcriptase polymerase chain reactions. Th1/Th2 chemokine levels in BAL fluid of idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP) were examined to evaluate the clinical relevance of Th1/Th2 chemokines.


RESULTS
The lung fibroblasts were polarized to produce Th1-type chemokines by the pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha and the anti-fibrotic cytokine, interferon (IFN)-gamma. However, the induction patterns of chemokines by these two cytokines were different, i.e., involving predominant induction of IP-10 and I-TAC by TNF-alpha and induction of Mig by IFN-gamma. Although Mig, IP-10, and I-TAC were produced within the BAL fluid of patients, TARC and MDC were at significantly low levels.


CONCLUSIONS
Our results suggest that lung fibroblasts tend to induce a Th1-type immune response under normal conditions, and that a Th2-type immune response does not play a significant role in smoldering inflammation around the established lesions in IPF and NSIP.
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Atsushi
A
Sumida
Yoshinori
Y
Hasegawa
Masakazu
M
Okamoto
Naozumi
N
Hashimoto
Kazuyoshi
K
Imaizumi
Hiroshi
H
Yatsuya
Toyoharu
T
Yokoi
Kenzo
K
Takagi
Kaoru
K
Shimokata
Tsutomu
T
Kawabe
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D018925:Chemokines; D012333:RNA, Messenger