Monitoring of pneumocystis jirovecii pneumonia by specialized pro-resolving mediators

Abstract

It is well described that ending inflammation is not a passive phenomenon only due to catabasis of pro-inflammatory mediators. Inflammation arrest is controlled by the synthesis of lipoxins, resolvins, protectins and maresins, which are actively involved in return to homeostasis (called resolution). Uncontrolled inflammation could then be due to a defect of resolution. Nothing is known on these mediators during Pneumocystis pneumonia (PCP), even if inflammation plays a major role in the pathophysiology of PCP. While necessary for the control and elimination of Pneumocystis jirovecii (the causative opportunistic fungus for PCP), the host's inflammatory response can therefore lead to lung damage and may explain PCP severe prognosis with high mortality rates.

Lipid profiling of patient plasma were done by a complex methodology using mass spectrometry, which allows concomitant detection and quantification of low-level inflammatory and resolutive lipid mediators.

Among the seven evaluated patients, inflammatory PGE2 was quantifiable in 4 patients, detected in 2 patients (under the limit of quantification (LOQ)) and not detected in 1 patient (under the limit of detection (LOD)). Lipoxin B4 (and its isomer), a specialized pro-resolving mediator, was quantifiable in 2 patients and under the LOQ but detectable in the 5 remaining patients, suggesting that LXB4 is synthesised during PCP. RvD1 and RvD2, two others mediators known for actively stopping inflammation, were undetectable in all the patients.

Results of this pilot clinical study might thus orientate towards a defect of the control of inflammation during PCP due to a clear lack of synthesis of D1 and D2 resolvins.