Previously observed decreases in blood gelsolin levels in different medical conditions associated with an inflammatory response or parenchymal tissue damage indicate that this protein might function as a regulator of the innate immune response [5
]. In agreement with those previous studies we found that 2 etiopathologically different infections affecting the CNS, such as LNB and TBE (caused by bacterial and viral pathogens, respectively) lead to alteration of gelsolin levels in blood. More precisely, our study reveals an approximately 20–50% lower blood gelsolin concentration in LNB and TBE patients compared to control subjects. However, the cause of the lower blood gelsolin levels is unclear, and at this point it is only possible to provide a hypothetical explanation. Firstly, it is possible that axonal damage with actin release within the intrathecal compartment, which takes place in CNS tissue during LNB or TBE development, may increase a demand for gelsolin that results in its depletion from the blood [18
]. Such an increased demand would account for the decrease in gelsolin in the blood, assuming that normal blood levels cannot be maintained by increased production, which in the case of plasma gelsolin occurs mainly in muscle cells [19
]. Secondly, it can be hypothesized that neuronal release of actin within the CNS will cause mobilization and accumulation of gelsolin in the CNS. An increase in CSF gelsolin levels may also be expected due to blood-CSF barrier dysfunction, which usually accompanies LNB and TBE [20
]. However, the latter possibility is less likely since we did not observe significantly higher intrathecal levels of gelsolin in the CSF of LNB and TBE patients, as could be expected, based on the gelsolin concentration gradient between blood and CSF. However, the fact that diagnostic lumbar puncture was performed at an early stage of the disease, which usually is not accompanied by severe disruption of the blood-CSF barrier [20
], and the possibility that gelsolin-F-actin complexes might be lost during centrifugation to prepare CSF samples could both impair the interpretation of the data.
Despite being of completely different etiology (bacteria vs. RNA virus), the changes in blood and CSF gelsolin concentrations in LNB and TBE patients were similar. This finding suggests that some common mechanisms engaged in an inflammatory process are responsible for the gelsolin depletion. The innate immune system response, composed of various cell types sharing antigen recognition ability, which is the earliest defence against all pathogens, may provide a molecular basis for the observed gelsolin decrease [22
]. Because of the similarity between multiple sclerosis and LNB chronic inflammation, it might be expected that the same molecular mechanism is responsible for blood gelsolin depletion in multiple sclerosis and LNB patients [8
]. Since there is a great variety of innate immune molecular factors, it is difficult to establish which ones are responsible for this reaction [11
]. Therefore, plasma gelsolin should be considered a marker of inflammation due to its observed decrease in various conditions associated with tissue injury not limited to infectious causes [26
Our findings are also in agreement with previous suggestions concerning gelsolin function. Gelsolin is a multifunctional protein that can bind various bioactive lipids and influence an immunological host response to serious injury. Gelsolin binds not only eukaryotic, but also prokaryotic lipids of Gram-positive and Gram-negative bacteria [3
]. Biologically active phospholipids are an important component of the spirochete B. burgdorferi
outer membrane, which contains a lipopolysaccharide-like substance that could potentially interact with gelsolin [11
]. On the other hand, the pathogen causing TBE is an enveloped virus (Flaviviridae family) with an RNA genome that does not contain any known active phospholipids. In all cases of CNS infections, independent of their etiology, an array of inflammatory mediators is produced, including platelet-activating factor and sphingosine-1-phosphate [1
]. Both of these have a number of proinflammatory properties and are implicated in the pathogenesis of a number of diseases, ranging from an allergic reaction to neurodegenerative disorders such as multiple sclerosis [8
Our findings, which indicate depletion of gelsolin as a step in the pathophysiology of an inflammatory response to B. burgdorferi and TBE virus infections, suggest that administration of recombinant plasma gelsolin warrants consideration as a new therapeutic strategy for these diseases. Further long-term studies are required to evaluate the prognostic value of gelsolin level analysis as a biochemical marker for predicting and monitoring neurological decline in the course of LNB and TBE. It is possible that gelsolin evaluation in combination with other biomarkers can increase diagnostic accuracy and better assessment of CNS infections.