Community acquired pneumonia (CAP) is one of the most common infections with unfavourable outcome. Changes of serum lipid profile in CAP including a decrease in sphingomyelins and an increase in ceramides (Cer) and acid sphingomyelinase (SMPD1) were shown, but consequences thereof are unknown.

In order to test for consequences of increased SMPD1 activity and sphingolipid alterations, we analysed the sphingolipid profile and activity of 168 sera and 101 whole blood samples from CAP patients. Samples were also analysed for the presence and efficacy of functional inhibitors of SMPD1 (FIASMA).

In an age- and sex-matched cohort of CAP patients with varying severity at onset of hospitalisation, the extracellular activity of SMPD1 and sphingolipid changes were determined in comparison to 30  healthy controls (HC) by liquid chromatography coupled to triple-quadrupole mass spectrometry, presence of FIASMA by LC to high-resolution benchtop orbitrap MS. Correlations with clinical parameters were evaluated using multivariate regression analyses.

SMPD1 activity in CAP (291.8 pM/(mLxh)) was twice as high than in HC (144.7). In 56 sera with at least one FIASMA SMPD1 was significantly lower than in untreated patients. In CAP patients we found a significant decrease in sphingomyelin with concomitant increase in corresponding Cer and its monohexylated form, presumable influencing pathophysiological processes.

Our stud confirmed an increased SMPD1 activity in CAP. FIASMA treated patients demonstrated significantly reduced activity. Beside correlation with severity markers, subsequent effects on membrane composition and formation of monohexylated Cer may play a role in CAP progression.