Immunoregulatory properties of vasoactive intestinal peptide in human T cell subsets: implications for rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease whose pathogenesis is not completely understood. Unbalanced Th1/Th2 T-cell polarization has been suggested to play a pathogenetic role and therefore, modulation of T-cell polarization is a potential therapeutic target. Vasoactive intestinal peptide (VIP) is a broadly distributed peptide that exerts anti-inflammatory and immunomodulatory effects, in the collagen-induced arthritis (CIA) murine model of RA, and ex vivo, in synovial cells from RA patients. In the present study, we have found that polyclonal stimulation of peripheral blood lymphocytes (PBL) from RA patients produces higher levels of inflammatory mediators and lower levels of Th1 cytokines than PBL from healthy controls; moreover, VIP has negligible effects on inflammatory mediators and Th1 cytokines produced by PBL from healthy controls but favours Th2 profile and enhanced IL-10 production after stimulation. VIP increases the levels of IL-10 and IL-4 in the supernatant of human CD4(+)CD45RA(+) cells cultured in a non-conditioned or a Th2-conditioned situation. In contrast, VIP does not modify the production of these cytokines in a Th1-conditioned medium. In summary, VIP can differentially modify the functional capacity of human lymphocytes by inducing Th2/Treg differentiation depending on their previous phenotype.
Gutiérrez-Cañas
Irene
I
Departamento de Biología Celular, Facultad de Biología, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Juarranz
Yasmina
Y
Santiago
Begoña
B
Martínez
Carmen
C
Gomariz
Rosa P
RP
Pablos
José Luis
JL
Leceta
Javier
J
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000037:antagonists & inhibitors; D006801:Humans; D007107:Immune System / Q000502:physiology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D016753:Interleukin-10 / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D016753:Interleukin-10; D014660:Vasoactive Intestinal Peptide