G. Mccormack et al., In-vitro cyclosporin sensitivity of proliferating lymphocytes is predictive of in-vivo therapeutic response in ulcerative colitis, ALIM PHARM, 15(5), 2001, pp. 665-668
Background: The efficacy of cyclosporin in the management of ulcerative col
itis is recognized. Not all patients respond to this treatment. Existing cl
inical and laboratory parameters are of little use in identifying those mos
t likely to respond.
Aims: To determine whether in-vitro sensitivity to cyclosporin as measured
by a lymphocyte proliferation assay is predictive of in-vivo response to th
erapy,
Methods: The study comprised seven responders with ulcerative colitis, seve
n non-responders, and 14 healthy matched controls. A lymphocyte proliferati
on assay was carried out in the presence of a range of concentrations of cy
closporin and a dose-response curve constructed for each subject. The IC50
value, the concentration of cyclosporin that resulted in 50% inhibition of
proliferation, was calculated for each subject. IC50 values for responders,
non-responders and controls were compared using a Mann-Whitney test.
Results: There was a wide range of values obtained for the study group as a
whole, IC50 values for nonresponders were significantly higher than those
of responders (P < 0.05).
Conclusions: There is a population-wide variation of in-vitro sensitivity t
o cyclosporin. This is reflected in in-vivo sensitivity as measured by clin
ical response to cyclosporin treatment. Future therapeutic strategies need
to address this inherent variability of individual response to therapy.