Can IL-4Ralpha and PAR-2 in bronchoalveolar lavage fluid serve as biomarker of fibroproliferative healing in interstitial lung diseases?

Abstract

Aims: Prognosis and therapeutic approach to interstitial lung diseases (ILDs) depend on their tendency to fibroproliferative healing. In our previous works we proved a relationship of IL-4 gene polymorphisms and IL-4 receptor alpha (IL-4Ralpha) and proteinase activated receptor (PAR-2) expression in lung tissue in fibrotic idiopathic interstitial pneumonias (fIIPs) and increased values of IL-4Ralpha and PAR-2 in bronchoalveolar lavage fuid (BALF) in chronic hypersensitivity pneumonitits(HP). Thus we aimed to compare the PAR-2 and IL-4Ralpha BALF values in different ILDs to test whether these molecules might serve as biomarkers of fibroproliferative healing.

Methods: BALF samples of 46 patients with ILDs (8 sarcoidosis (SARC), 15 HP, 13 fIIPs and 10 ILDs within connective tissue diseases (ILD-CTD)) were investigated by ELISA method to detect PAR-2 and IL-4Ralpha values. The Kruskal-Wallis test with multivariate comparisons was used to compare the PAR-2 and IL-4Ralpha values between the ILDs subgroups.

Results: There was no significant difference of BALF IL-4Ralpha values between the ILDs (P=0.2729,NS). For PAR-2 we found significantly lower BALF concentrations in SARC compared to other ILDs (mean values in pg/ml: HP 19.93;fIIPs 26.0;ILD-CTD 27.5;SARC 9.3; P=0.007). In multivariate comparison the PAR-2 values in the HP, fIIPs and ILD-CTD groups differed significantly from SARC and on the contrary SARC differed significantly from all (p<0.05).

Conclusion: We hypothesize that PAR-2 in BALF might be a potential biomarker of fibroproliferative healing and can help in differential diagnosis of ILDs with/without progressive fibroproliferative healing.