In autoimmune diseases, inflammatory cytokine concentrations are important for initiating
and maintaining the status of autoimmunity. Autoimmune hepatitis (AIH) is an inflammatory
liver disease characterized by a loss of immune tolerance against specific antigens
located in hepatocytes. During the progression of the disease, antigen-presenting
cells and different classes of T-helper cells secret specific cytokines important
for maintaining the disease.
As these cytokines are secreted into the local liver environment, the blood flow in
liver sinusoids might influence the local cytokine concentration. Considering the
liver tissue as a porous medium, based on Darcy's law, the microcirculation within
a liver lobule was modelled. Using realistic physiological pressure differences and
tissue permeabilities, the blood velocity inside the sinusoids could be calculated
and validated with blood velocity data obtained via Orthogonal Polarization Spectral
Imaging (OPSI). Furthermore, oxygen consumption is modelled to obtain Rappaport's
acinus model. Finally, steady state spatial distributions of secreted cytokines within
the liver lobule could be estimated for specified realistic production rates of T-helper
cells.
It could be demonstrated that the characteristics of the liver microcirculation might
have an important impact on establishing inflammatory cytokine levels within the portal
fields and the vascular septa promoting the occurrence of interface hepatitis.
Corresponding author: Lettmann, Karsten A.
E-Mail:
lettmann@icbm.de
