Cytokine production in Linomide-treated nod mice and the potential role of a Th (1)/Th(2) shift on autoimmune and anti-inflammatory processes.
Linomide prevents the development of autoimmune insulitis and insulin-deficient diabetes mellitus in female NOD mice. Linomide prevents development of autoimmune manifestations in other experimentally induced and spontaneous autoimmune diseases as well, but the mechanism of action is unknown. The present report summarizes our investigations on the effect of Linomide on different functional T cell subsets in NOD mice analyzed according to their cytokine profile. Supernatants from cultured splenocytes and peritoneal cells taken from Linomide-treated mice contained lower levels of TNFalpha, IL-1 beta, IFN gamma and IL-12 versus higher levels of IL-4, IL-6 and IL-10 in comparison with supernatants from cultures of untreated mice. Our results suggest that regulation of autoimmunity following oral Linomide administration in NOD mice induces a shift from Th(1) to Th(2) phenotype response, thereby preventing the development of diabetes by active cytokine-induced immunoregulation of T cell subsets, including downregulation of Th(1) and upregulation of Th(2).
Departments of Bone Marrow Transplantation & Cancer Immunotherapy, Hadassah University Hospital, Jerusalem, Israel.
Lola
L
Weiss
Vivian
V
Barak
Michael
M
Zeira
Ali
A
Abdul-Hai
Israel
I
Raibstein
Shoshana
S
Reich
Esther
E
Hirschfeld
David
D
Gross
Shimon
S
Slavin
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006912:Hydroxyquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D016688:Mice, Inbred NOD; D013154:Spleen / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D006912:Hydroxyquinolines; D003208:Concanavalin A; C045282:roquinimex