SIGNIFICANCE OF ELEVATED PROCOLLAGEN-III-PEPTIDE AND TRANSFORMING GROWTH-FACTOR-BETA LEVELS OF BRONCHOALVEOLAR LAVAGE FLUIDS FROM IDIOPATHIC PULMONARY FIBROSIS PATIENTS

Although both procollagen III aminopeptide (P-III-P) and transforming growth factor-beta (TGF-beta) are reported to be present in lung tissu e and/or elevated in bronchoalveolar lavage fluid (BALF) from idiopath ic pulmonary fibrosis (IPF) patients, me have little knowledge concern ing the clinical significance of elevated P-III-P and TGF-beta levels in BALF. Using a radioimnunoassay, we measured P-III-P and TGF-beta in BALF from 48 IPF patients (16F and 32M, 59+/-2 years, mean+/-S.E.) wh o received BAL in our clinic over the past 13 years before glucocortic osteroid treatment. Among them, we could detect a significant amount o f P-III-P (2.2+/-1.0 U/ml; range 0.03 to 16.5 U/ml) in BALF in 18 of t he patients (5F and 13M, 58+/-3 years) (group B), but not (0.03 U/ml o r less) in the other 30 patients (11F and 19M, 59 +/- 2 pears) (group A). Lymphocyte (%) and basophil (%) in BALF from group B wad; much lar ger than that from group A (33% vs. 8%, p<0.01). Group B showed a long er duration of onset to BAL (36 months vs. 23 months, p<0.05). TGF-bet a levels were obtained using an ELISA system kit from the same BALF sa mples. TGF-beta was not detected in 10 patients (100 pg/ml or less) (3 F and 7M, 59+/-4 years) (group I), while the remaining 38 patients sho wed a significant amount of TGF-beta (329+/-44 pg/ml, range 100 to 1,3 60 pg/ml). The latter patients were further divided into two groups; g roup II 100 to 300 pg/ml (10F and 14M, 56+/-3 years) and group III 350 or more (3F and 11M, 63+/-2 years). Group III showed significantly be tter values in PaO2, Aa-DO2, %VC and %DLco, and smaller percentage of basophils in BALF than did groups I and/or II, whereas survival after BAL in group III was significantly shorter than in group I (31 vs. 19 months, p<0.05). There was no significant relationship between P-III-P and TCF-beta levels in BALF. These findings suggest that elevated P-I II-P level is accompanied by an increase in lymphocyte population in B ALF from IPB patients, resulting in a longer duration of the disease, while elevated TGF-beta level reflects alveolar inflammation at an ear lier stage of the disease which induces a progression of the disease, resulting in a shorter survival in IPF patients.