Significant Upregulation of BAL-f IL-1 beta in Lung Transplant Recipients During Stability and CLAD

Purpose

Previous studies aimed to evaluate cytokine profile of Broncho-alveolar Lavage Fluids in Lung Transplant recipients (LTxR) during stability or during complications such as infections or rejection showed that no specific profile correlates with acute rejection while during Infectious episode. Aim of our study was to assess the signature of pro-inflammatory and interferons in LTxR in stable clinical conditions in absence of Infections and rejection.

Methods

Ten BALf of stable LTxR were analyzed by a multiplex bead-based immunoassay to evaluate twelve cytokines (IL-1β; IL-6; CXCL10; TNFα; IFN-λ1; IL-8; IL-12; IFN-α2; IFN-λ2,3; IFN-β; IL-10; IFN-ϒ). The results obtained were compared to a sample of IPF patients (n°10), Obstructive CLAD LTR (BOS n°6) and healthy controls (HC, n°3). All samples were included after exclusion of concomitant sign/symptoms of infection. In a subsample of LTR (n°10) and IPF (n°10) IL1-β mRNA expression levels were analyzed on BAL cells.

Results

Among all tested cytokines only IL-1β and IL-8 resulted significantly dysregulated among study groups. In fact, we observed that stable LTxR showed higher IL-1β (1.04; 0, 3.915) and IL-8 (43.74; 24.29, 205.5) in BALf compared to HC and IPF affected patients (p < 0.05). The result of IL-1β was confirmed also by the analysis of mRNA in cells of respective BAL. Comparing IL-1β and IL-8 in BALf of stable LTxR and BOS-affected patients, IL-1β was significantly higher in BOS patients (6.81; 2.5, 24.71), while no significant variation was found for IL-8.

Conclusion

While previous report showed a significant association between Infections and IL-1β and IL-8 levels in LTxR, we demonstrate that there is a significant upregulation of these cytokines also in stable condition with respect to HC and also with respect to a pro-fibrotic lung disease (IPF). In addition, IL-1β increases significantly in patients developing BOS, thus suggesting a possible pathogenic role and therapeutic target