[The Serum Levels of Cytokines in Patients with Rheumatoid Arthritis Associated Interstitial Lung Disease and Their Clinical Significance]

Objective: To study the clinical significance of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases (TIMPs) and transforming growth factor beta 1 (TGF-beta1) in the serum of patients with rheumatoid arthritis (RA) associated interstitial lung disease (ILD).

Methods: Twenty-nine patients with RA only (the RA group) and 28 patients with RA associated ILD (the RA-ILD group) were included in the study. Patients in the RA-ILD group were divided into 2 subgroups, 16 in the early RA-ILD group and 12 in the late RA-ILD group. Twenty-nine healthy volunteers served as the control group. ELISA was used to detect the levels of MMP-9, TIMP-1, TGF-beta1 in the serum of the three groups.

Results: The TIMP-1 levels of both the RA and the RA-ILD groups [(645 +/- 220) microg/L, (536 +/- 188) microg/L] were significantly higher than that of the control group [(392 +/- 92) microg/L, F = 15.221, P < 0.01]. The TGF-beta1 level of the RA-ILD group [(13.1 +/- 10.0) microg/L] was significantly higher than those of the control group and the RA group [(3.9 +/- 2.9) microg/L, (2.4 +/- 1.7) microg/L, F = 26.455, P < 0.01]. There was no difference in the TIMP-1 level between RA-ILD and RA groups, the TGF-beta1 level between the control group and the RA group, the MMP-9 level and MMP-9/TIMP-1 ratio among the three groups. The TIMP-1 level in the late RA-ILD group [(690 +/- 110) microg/L] was higher than that of the early RA-ILD group [(420 +/- 147) microg/L, t = -5.347, P < 0.01]. The TGF-beta1 level in the late RA-ILD group [(17.9 +/- 8.2) microg/L] was higher than that of the early RA-ILD group [(9.5 +/- 9.9) microg/L, t = - 2.39, P < 0.05]. The MMP-9/TIMP-1 ratio of the late RA-ILD group (0.9 +/- 0.1) was lower than that of the early RA-ILD group (1.2 +/- 0.4, z = 4.307, P < 0.01). There was no statistic significance in the MMP-9 level between the early and the late RA-ILD groups [(537 +/- 309) microg/L, (595 +/- 110) microg/L, t = - 1.397, P = 0.174].

Conclusions: TGF-beta1, can be used as a diagnostic marker of ILD in RA patients and it also reflects the pathological change of the lung. The decrease of MMP-9/TIMP-1 ratio in RA patients with ILD can reflect the severity degree of lung pathological changes.