TNF α‐induced leukocyte–endothelial cell interactions show marked interindividual differences independent of the clinical response to adalimumab

Abstract

The responses of patients with psoriasis to TNFα-antagonists show interindividual differences. Here, TNFα-incubation induced endothelial adhesion molecules, a prerequisite for leucocyte recruitment to inflamed tissues. Using a standardized flow chamber system equipped with near-confluent endothelial cells and a mobile phase containing human leucocytes, proportions of leucocytes interacting with endothelial cells were remarkably different between individual donors (up to 3.5-fold), regardless of whether the leucocytes originated from patients with psoriasis (n=10) or healthy donors (n=10). Adalimumab abrogated adhesion molecule induction and interactions with leucocytes when present prior to or simultaneously with, but not after exposure of the cultures to TNFα. This pattern was seen similarly with leucocytes from healthy donors (n=4), and patients whose psoriasis responded well to adalimumab (n=5) and non-responders (n=5). Thus, although considerable interindividual differences of leucocyte-endothelial cell interactions were demonstrated ex vivo in a TNFα-governed microenvironment, such differences are not associated with individual responses to treatment with adalimumab in vivo.