TNF α-induced leukocyte-endothelial cell interactions show marked interindividual differences independent of the clinical response to adalimumab.
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.
Department of Dermatology, Venereology and Allergology, University Medical Center, Georg August University, Göttingen, Germany.
Anike
A
Lockmann
Michael P
MP
Schön
D000068879:Adalimumab; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000473:pathology; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab
TNF antagonists; endothelial cells; leukocytes; psoriasis