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

Chung-Wei Chou,Han-Chen Tsai,Fang-Chi Lin,Shi-Chuan Chang

doi:10.1186/1471-2466-14-182

Abstract

BackgroundConcurrent 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.MethodsWe measured pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-17, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-β1 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 β-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.ResultsCompared with pure PJP group, mixed PJP group had significantly higher BALF levels of IL-1β, TNF-α and IL-8 and significantly higher blood levels of IL-8. The BALF ratios of TNF-α/IL-10, IL-8/IL-10, IL-1β/IL-10, TNF-α/TGF-β1, IL-8/TGF-β1, IL-1β/TGF-β1 and IL-1β/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-1β/TGF-β1, MCP-1/TGF-β1, MCP-1/IL1RA and IL-8/TGF-β1 were found in the patients requiring mechanical ventilation and in non-survivors.ConclusionsIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2466-14-182) contains supplementary material, which is available to authorized users.

Highlights

Concurrent infection may be found in Pneumocystis jirovecii pneumonia (PJP) of non-acquired immunodeficiency syndrome (AIDS) patients, its impact on immune dysregulation of PJP in non-AIDS patients remains unknown
The oxygenation index, Acute Physiology and Chronic Health Evaluation II scores, intensive care unit (ICU) length of stay, the percentage of ICU admission, use of ventilator and death showed no significant differences between the pure PJP and mixed PJP patients
The results showed no significant differences in the variables measured except for that bronchoalveolar lavage fluid (BALF) IL-1β/IL-1 receptor antagonist (IL-1RA) ratio were significantly higher in bacterial infection group

Summary

Introduction

Concurrent infection may be found in Pneumocystis jirovecii pneumonia (PJP) of non-acquired immunodeficiency syndrome (AIDS) patients, its impact on immune dysregulation of PJP in non-AIDS patients remains unknown. PJP-related morbidity and mortality appear to be a major health problem for patients with acquired immunodeficiency syndrome (AIDS) and for those with immunosuppression resulted from chemotherapy, organ transplantation and long-term treatment with steroid or other immunosuppressants for a variety of diseases [1]. The clinical features, radiological findings, response to treatment and outcome of PJP are reported to be widely different between the patients with or without AIDS [2,3]. The reasons underlying the differences in clinical features, radiological findings, treatment response and outcome of PJP between the patients with and without AIDS remain to be elucidated. Our and previous studies [9,10] indicated that immune dysregulation was found in PJP of the patients with AIDS and non-AIDS, and certain pro-inflammatory cytokine/ anti-inflammatory cytokine ratios in bronchoalveolar lavage fluid (BALF) were of considerable value in assessing the severity of PJP and outcome of the patients [10]

Methods

Results

Discussion

Conclusion