Shunt infection may be associated with the number of shunt revisions, patient age, manual shunt system, and exposure to surgical instruments. The overall incidence amounts to 3–15% of all implanted shunt systems [
2,
8,
12,
14,
20,
21]. Ninety percent of all microorganisms infecting CSF shunting devices belong to
Staphylococcus and
Streptococcus species [
1,
17]. The clinical material was notable for an increase in pleocytosis from the very beginning of known infection, in which the dysfunction of infected shunt was present [
5,
17,
22]. This observation is totally at odds with the results described in the present article. Indeed, no visible increase in pleocytosis was not observed in the study group. Eosinophilia may be present very often in bacterial infection [
17,
19,
22]. In the study group, the highest level of eosinophils in peripheral blood was observed at the time of the second measurement (Fig.
1). The same tendency was observed in the analysis of blood cell differential count (Fig.
2). It is possible that the increase in eosinophils in the study group could account for the highest CSF pleocytosis values observed in the second measurement (Fig.
3). Eosinophilia in CSF was defined as ≥ 5% or according to other authors ≥ 10% eosinophils in the CSF [
5,
17,
22] Eosinophils in the CSF are not particularly specific for bacterial encephalitis, which is more likely to be associated with CSF neutrophilia [
10]. This reaction could be responsible for an early increase in CSF protein levels observed in the study group (Fig.
4). Eosinophilic encephalitis is more typical for parasitic infections, e.g.,
Angiostrongyliasis cantonensis (~ 70% of patients) and
Gnathostoma spinigerum (> 55% of patients). Other infections with a concomitant eosinophilic reaction may include different microorganisms, such as helminths, fungi, bacteria, and viruses [
6,
11,
22]. An allergic reaction could be another causative agent in eosinophilic encephalitis. The main reason for an increase in CSF eosinophil levels after shunt implantation is still unknown. The increase in eosinophils could be present when the CSF was free from bacterial contamination or in the absence of shunt dysfunction [
17]. It is surprising that in the presented material, the peak level of eosinophils in peripheral blood was reached after microbial elimination. A possible explanation could be related to the ability of
Staphylococcus species to form the so-called biofilms [
21]. This structure is responsible for interaction with the immunological environment. Therefore, it is possible that despite the absence of bacterial strains in the CSF, they are still present on the surface of intraventricular catheters [
21]. The whole process for the migration and activation of eosinophils in patients with ventriculoperitoneal shunts as a result of either infection or allergy is fully described [
17]. As it has been mentioned at the beginning of the article, in contrast to neutrophils and monocytes, eosinophils have an ability to adhere well to shunt catheters [
22]. That ability could play an important role in the case of intraventricular catheter contamination by
Staphylococcus species [
17,
19]. Another explanation for eosinophilic activation may be shunt obstruction accompanying shunt infection [
17]. In addition, residual CSF in the chamber of the occluded shunt system could trigger an allergic reaction [
5]. Unfortunately, this process does not explain the culmination of eosinophilia in peripheral blood at second measurement, because at that time, infected shunts were removed. This procedure is consistent with the established operative protocol in the context of shunt infections and is performed by many clinicians [
1,
2,
20‐
23]. The third presumed cause of an allergic reaction to shunt infection could be reaction to intraventriculary administered antibiotic therapy [
1,
19]. Particularly, vancomycin overdose could be responsible for the eosinophilic reaction [
1]. The authors agree that maximal therapeutic effectiveness could be achieved when vancomycin concentrations in CSF reach the level of 5–10 μg/mL. CSF output from a ventricular system could influence the concentration of administered vancomycin. CSF is completely exchanged three to four times per day on average. Patients with ventriculitis may have decreased clearance of vancomycin secondary to a fall in CSF production. Theoretically, CSF vancomycin concentrations < 5 and > 10 μg/ml are out of therapeutic window [
1]. In the presented clinical material, Vancocin was intraventricularly administered according to the same time dose regimens up to the shunt implantation, so there is no explanation to decrease of the level of eosinophils just before shunt implantation [
17]. The significant differences in the level of eosinophils in blood between the control and study groups could be an allergic reaction to implanted artificial material like intraventricular catheters (Figs.
1 and
2). Eosinophilia as an allergic reaction could be disclosed relatively late 8 months after shunt implantation [
4,
22]. The control group is free from the allergic reaction due to shunt implantation. But regarding the role of immunization of implanted material, there is still unknown why the eosinophils decrease in the study group in the third measurement (Figs.
1 and
2). In that group, intraventricular catheter is always present in the lumen of cerebral ventricles and should exert constant stimulation to allergic reaction. An eosinophilia in the peripheral blood could be a reaction to the bleeding during shunt removal too. It is observed in the case of subarachnoid bleeding [
4]. But in the study group, patients after bleeding into ventricular system were excluded. In order to understand eosinophilic encephalitis induced by shunt infections, sometimes analogies of other diseases are found [
16]. There is no natural presence of such morphotic elements like leucocytes in the CNS because of the blood–brain barrier (BBB) mechanism existence. So the central nervous system is the place of immune privilege [
7,
21]. The innate morphotic elements of immunologic reaction in CNS are the following: microglial cells, infiltrating myeloid cells, astrocytes, oligodendrocytes, and NG2+ glia (also termed polydendrocytes or oligodendrocyte progenitor cells) [
7,
21]. Microglia progenitors enter the CNS at embryonic day 9.5–10.5 [
7,
21]. In the CNS, pro-inflammatory cytokines like IL-1, IL-6, TNF-α, and INF-β are produced by resident cell and are less migrated by lymphocyte. The sources of cytokines are the following: cerebrovascular endothelial cells, microglia, and astrocytes [
21]. In the material, it was checked the level of IL-6 in the cerebrospinal fluid. Similarly to eosinophils, the second measurement reached the highest level in the analysis. Contrary to the eosinophilia, the third measurement was the same as that in the control group (Table
1). IL-6 starts in the inflammation process and takes part in the erythropoiesis and many allergic reactions [
15]. The role which acts by IL-6 could explain the observed level dynamism in CSF. So it exposes the role of innate morphotic response in the central nervous system. Clinical material presented in the article comprises other elements of the observed humoral immunological response. The next one was IL-5 measured in the cerebrospinal fluid (Table
1). IL-5 could stimulate the production of eosinophils from pluripotent bone marrow stem cells and their release to circulation too. This interleukin is produced by Th2-type helper lymphocytes in response among others to allergies. Mature eosinophils adhere to endothelial cells and migrate into the tissues after exposure to this chemoattractant. So, the level of IL-5 in the cerebrospinal fluid depicted the peripheral immunological response [
15,
17]. The elevated level of IL-5 lasts longer in the study group than that of IL-6, because it is a visible increase of this lymphokine through the whole period of observation (Table
1). The role of that agent in the allergic reaction is proved by works describing role of corticosteroids in promotion of ventriculoperitoneal shunt survival by blocking the effect of eosinophil meaning as production, migration, and/or granule release, by inhibiting the production and/or release of IL-5 in the bone marrow, and preventing chemoattractant production and upregulation of adhesion molecules [
17]. The assumption that increased level of CSF pleocytosis in the second measurement is connected with the level of eosinophils in the peripheral blood is supported by chemoattractant dynamism in CSF observed in the clinical material (Table
1). The peak level in CSF of receptor for eotaxin (CCL-11), small cytokine belonging to the CC chemokine family, was obtained in the first and second measurements, and it was significantly higher than that in the third measurement and in the control group (Table
1). CCL-11 selectively recruits eosinophils by inducing their chemotaxis. It is a component of allergic response [
13]. Another strong chemoattractant analyzed in the clinical material receptor for eotaxin (CCL-26) remained increased in the study group through the whole period observation. It was also significantly higher than that in the control group. It could be possible that it is a natural antagonist for CC chemokine receptors 1 and 5 of human chemokine and acts rather a regulatory role in the observed allergic reaction [
13]. Finally, it was examined the level in CSF of CCL-3(chemokine) and MBP (myelin granule protein) both produced by eosinophils [
9] (Table
1). The highest level of both substances in CSF was obtained in the study group in the second measurement. The result strongly suggests that observed pleocytosis in CSF could be composed from eosinophils.
Table 1
The analyzed lymphokines and proteins in the study group and in controls. C, control group, I—measurement I, II—measurement II, III—measurement III
CCL26/Eotaxin-3 | 7.97 | 6.86 | 7.59 | 4.40 | C < I= II = III |
IL-5 | 1.51 | 1.84 | 1.65 | 0.56 | C < I = II = III |
IL-6 | 320.39 | 555.05 | 50.60 | 46.35 | C = III < I < II |
CCL11/Eotaxin-1 | 21.68 | 16.79 | 9.64 | 5.60 | C < III < I = II |
CCL3/MIP-1a | 1.65 | 27.28 | 15.60 | 17.84 | II > C > III > I |
MBP | 0.01 | 1.60 | 1.83 | 0.52 | I < = II = (C < III) |