The impact of concomitant pulmonary infection on immune dysregulation in Pneumocystis jirovecii pneumonia

Background: Concurrent infection may be found in Pneumocystis jirovecii pneumonia (PJP) of non-acquired immunodeficiency syndrome (AIDS) patients, however, its impact on immune dysregulation of PJP in non-AIDS patients remains unknown. Methods: We measured pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-8, IL-17, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-beta 1 and IL-1 receptor antagonist (IL-1RA) and inflammatory markers including high mobility group box 1, Krebs von den Lungen-6, receptor for advanced glycation end product, advanced glycation end product, surfactant protein D in bronchoalveolar lavage fluid (BALF) and blood in 47 pure PcP and 18 mixed PJP and other pulmonary infections (mixed PJP) in non-AIDS immunocompromised patients and explored their clinical relevance. The burden of Pneumocystis jirovecii in the lung was determined by counting number of clusters of Pneumocystis jirovecii per slide and the concentration of beta-D-glucan in BALF. PJP severity was determined by arterial oxygen tension/fraction of inspired oxygen concentration ratio, the need of mechanical ventilation and death. Results: Compared with pure PJP group, mixed PJP group had significantly higher BALF levels of IL-1 beta, TNF-alpha and IL-8 and significantly higher blood levels of IL-8. The BALF ratios of TNF-alpha/IL-10, IL-8/IL-10, IL-1 beta/IL-10, TNF-alpha/TGF-beta 1, IL-8/ TGF-beta 1, IL-1 beta/TGF-beta 1 and IL-1 beta/IL-1RA were significantly higher in mixed than in pure PJP patients. There was no significant difference in clinical features and outcome between pure and mixed PJP groups, including inflammatory biomarkers and the fungal burden. In pure PJP patients, significantly higher BALF levels of IL-8 and the ratios of IL-8/IL-10, IL-1 beta/TGF-beta 1, MCP-1/TGF-beta 1, MCP-1/IL1RA and IL-8/ TGF-beta 1 were found in the patients requiring mechanical ventilation and in non-survivors. Conclusions: In summary, concurrent pulmonary infection might enhance immune dysregulation of PJP in non-AIDS immunocompromised patients, but did not affect the outcome as evidenced by morbidity and mortality. Because of limited number of cases studied, further studies with larger populations are needed to verify these issues.