The effect of taurolidine on human blood cells

Intestinal failure and home parenteral nutrition:
Over the last decade, the number of patients with severe intestinal failure
(IF) in the Netherlands has exponentially increased up to 400 cases. Causes are
mainly extensive intestinal resections following inflammatory or vascular bowel
diseases that lead to short bowel syndrome, and motility disorders. IF patients
depend on life-long home parenteral nutrition (HPN). This is a complex
treatment that centers on the self-management of central venous catheters
(CVCs) at home. The challenge here is to prevent the most daunting
complications of this treatment, i.e. catheter-related bloodstream infection
(CRBSI) [1, 2].

Catheter-related bloodstream infections:
Despite all preventive measures, CRBSIs remain a frequent complication, with a
reported incidence in expert centers that ranges from 0.38 to 2.99 CRBSIs per
1000 catheter days, and accounts for approximately 70% of all HPN related
hospital admissions [1-3]. CRBSIs are a threat to both catheter- and patient
survival and may lead to permanent loss of vascular access in case of repeated
catheter loss, and hence provide an indication for small bowel transplantation.
This is a highly complex therapy with a worse prognosis compared to HPN
treatment [1, 2].
There are various risk factors of developing an CRBSI. One of the risks is the
formation of a biofilm inside the catheter.

Taurolidine
In patients with IF taurolidine is often used to reduce the incidence of CRBSI.
The working mechanism of taurolidine is based on a chemical reaction, in which
during the metabolism of taurolidine methyl groups are released. First, those
methyl groups induce cell death by destroying the cell wall. Second, they
adhere to the microorganism wall and thereby inhibit adhesion to the catheter
surface[4].
Resistance to taurolidine is rare in microorganisms, since the mechanism of
action depends on active methylol group generation [5]. All these
characteristics of taurolidine provides a high potency for broad use in the
clinic. Yet, the exact mechanism of action is not elucidated to date.

Several studies have shown a reduction in CRBSI*s [4, 6, 7]. Wouters et al.
showed a significant reduction in CRBSIs in the group of patients with new
catheters [4]. However despite administration of taurolidine to more than
13.000 patients, overall data on the effects of taurolidine on gene expression,
protein production and immune function remain surprisingly scarce [8].
Taurolidine is eventually metabolized into taurine, which modulates
intracellular calcium activity, a critical component in the priming and
activation of phagocytes. In a murine sepsis model, taurolidine increased the
functional activity of peritoneal macrophages[9]. Also, taurolidine seems to
prevent the depression of cellular immunity after an operative trauma, with a
maintained delayed-type hypersensitivity response and increased Kupffer cell
numbers after intraperitoneal administration in a rat model[10]. Other cellular
effects of taurolidine include the induction of cancer cell death through a
variety of mechanisms that in part remain unclear but at least comprise
enhanced apoptosis, inhibition of angiogenesis, reduced tumor cell adherence
and down-regulation of inflammatory cytokine release[11].

Taken together these notions above urged us to design a study protocol to
characterize the effects of taurolidine on gene expression, protein production
and various immune system functions in vitro and the mechanism of action.

To investigate the effects of taurolidine on human blood cells by
identification of gene expression, protein production and immune response.

Cohort study of healthy volunteers

Incidental findings (knowledge of being at risk for the development of
diseases), however the discovery of these incidental
findings is extremely small