Cytokine production by leukocytes of Papillon-Lefèvre syndrome patients in whole blood cultures

Papillon-Lefèvre syndrome (PLS) is characterised by aggressively progressive periodontitis combined with palmo-plantar hyperkeratosis. It is caused by "loss of function" mutations in the cathepsin C gene. The hypothesis behind this study is that PLS patients' polymorphonuclear leukocytes (PMNs) produce more proinflammatory cytokines to compensate for their reduced capacity to neutralize leukotoxin and to eliminate Aggregatibacter actinomycetemcomitans. Production of more interleukin (IL)-8 would result in the attraction of more PMNs. The aim of this study was to evaluate the cytokine profile in PLS patients' blood cultures. Blood was sampled from eight PLS patients (one female) from six families (antiinfective therapy completed: six; edentulous: two) with confirmed cathepsin C mutations and deficient enzyme activity. Nine healthy males served as controls. Whole blood cultures were stimulated with highly pure lipopolysaccharide (LPS) from Escherichia coli R515 and IL-1β plus tumor necrosis factor (TNF)-α. Thereafter, release of IL-1β (stimulation: LPS and LPS plus adenosine triphosphate), IL-6, IL-8, interferon-inducible protein (IP)-10, and interferon (IFN)-γ (stimulation: LPS, IL-1β/TNFα) were detected by ELISA. Medians of cytokine release were, with the exception of IP-10, slightly higher for PLS than for controls' cultures. None of these differences reached statistical significance. Increased production of IL-1β, IL-6, IL-8, IP-10, or IFNγ as a significant means to compensate for diminished activity and stability of polymorphonuclear leukocyte-derived proteases could not be confirmed in this study. Cytokine profiles in blood cultures may not be used to identify PLS patients.