02 BOOK OF ABSTRACTS .indd

Humoral response in pleural space to cancer,
inflammation and injury
Jaromir Kotyza 1 , Karin Bunatova 1 , Milo{ Pe{ek 2
1
Dept. of Biochemistry, Medical Faculty in Pilsen, Charles University, The Czech Republic;
2
Dept. of Pulmology, University Hospital in Pilsen, Charles University, The Czech Republic
Pleural fluids (effusions) are formed under a variety of pathological conditions in pleural
space. They deflate the lung and often require evacuation by thoracentesis. Although
pleural fluids have long been a subject of biochemical investigations, unambiguous
diagnostic criteria for major etiological effusion groups have not yet been established.
A popular Light’s criterion is only used to distinguish between exudative effusions and
effusions of haemodynamic origin (transudates), in general by the analyzing total protein
and lactate dehydrogenase. In the past two decades, numerous attempts have been made
to introduce different markers of inflammation, acute-phase proteins, tumor markers,
enzymes, including proteases and their inhibitors, cytokines and growth factors, aiming
to differentiate between at least two major etiological groups, i.e. paraneoplastic and
parainflammatory effusions. This effort has only been successful in part, presumably
due to overlapping specificities of individual analytes.
We have recently focused our attention to gelatinase B (MMP-9), a matrix
metalloproteinase associated with cancer progression, in combination with C-reactive
protein (CRP), an acute-phase protein reflecting an inflammation and tissue injury. We
have found significant differences among the major etiological groups in gelatinase
B, with the highest concentrations in parainflammatory exudates, intermediate in
paraneoplastic exudates, and the lowest in transudates. Interestingly, gelatinase
B was also upregulated within hours following therapeutic talc pleurodesis and
explorative thoracoscopy, an intervention causing pleural injury. In analyzed
pleurodesis and thoracoscopy samples progelatinase B values significantly correlated
with proinflammatory cytokines IL-6 and IL-8, with myeloperoxidase, and with
neutrophil count.
Despite statistical significance of progelatinase B in differentiating pleural effusions,
the analysis of paraneoplastic group (n=133) revealed a distinct heterogeneity, with a
minor portion of fluids reaching values typical for inflammation-associated effusions.
A subsequent sorting based on tumor histology showed increased levels particularly
in exudates associated with metastatic tumors. Pleural fluid progelatinase B values
in general correlated with pleural CRP. A strong correlation between pleural and
plasmatic CRP points to a local reflection of a systemic host response reaction.
This work was supported by Ministry of Health (Grant NR 7891-3), and by Research
Project MSM 0021620819, The Czech Republic
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