Objective: To investigate the effect of selective phosphodiesterase (PDE) 4 inhibitors on nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNFα) and interleukin-8 (IL-8) secreted by peripheral blood mononuclear cells (PBMCs) in patients diagnosed as rheumatoid arthritis with interstitial lung disease (RA-ILD).
Methods: PBMCs isolated from 15 healthy volunteers (group A) and 20 patients with untreated active RA-ILD (group B) were cultured in vitro. PBMCs from healthy subjects were considered as normal control. PBMCs from RA-ILD patients were divided into four groups with different treatment: blank group (B1), theophylline group (B2), selective PDE4 inhibitor rolipram group (B3), and glucocorticoid group (B4) with dexamethasone. The expression of NF-κB was determined by immunocytochemical staining, and the levels of TNFα and IL-8 in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA).
Results: (1) The activity of NF-κB and the levels of TNFα and IL-8 in group B1 were significant higher than that in group A (P < 0.01). Compared with group B1, three parameters above were similar to those in group B2 (P > 0.05), while group B3 and group B4 had significant decreased levels of three parameters (P < 0.01); IL-8 level in group B4 was significantly lower than that in group B3 (P < 0.05). (2) TNFα and IL-8 levels were positively correlated with NF-κB activity in group B (r = 0.902 and 0.735, P < 0.01 respectively). (3) The reduction of TNFα and IL-8 levels were positively correlated with reduction of NF-κB activity after intervention of rolipram in group B3 (r = 0.874, P < 0.01; r = 0.561, P < 0.05 respectively).
Conclusion: NF-κB activation and proinflammatory cytokines were involved in the pathogenesis of RA-ILD. selective PDE4 inhibitors may inhibit the production of inflammatory cytokines by inhibiting the activity of the transcription factor NF-κB in PBMC, thus inhibiting the inflammatory reaction of RA-ILD.