title: TH1/TH2 cytokine secretion of first degree relatives of T1DM patients.
abstract: Th1/Th2 cytokine imbalance has been demonstrated in Type 1 diabetes (T1DM) patients. We characterized the peak levels, secretory pattern and total cytokine production of the Th1 cytokines (IL-2 and IFN gamma) and Th2 cytokines (IL-4 and IL-10), by stimulated peripheral blood mononuclear cells of twenty six first-degree relatives of T1DM patients, and eleven matched controls. At enrollment, first degree relatives demonstrated a significant increase in peak and overall secretion of IL-2; P<0.01 and P<0.005 respectively and IL-4 cytokine; P<0.05 and P<0.01 respectively, as compared to normal controls. Their mean IFN gamma secretion increased significantly, P<0.05, after one year while their higher IL-2 and IL-4 secretion remained unchanged. Ab-negative and Ab-positive relatives demonstrated a similar cytokine secretion pattern. Four relatives all Ab positive, developed diabetes: Peak IL-4 levels were low in three and markedly decreased within one year in one of these relatives, while peak IL-2 and IFN gamma levels were elevated in all of them. These data demonstrate that secretion of both Th1 and Th2 cytokines is increased in first-degree relatives of T1DM patients independently of their diabetes-associated autoantibodies. The presence of low IL-4 and elevated IL-2 and IFN gamma levels in autoAb positive relatives is associated with progression to overt disease.
authors.affiliation: Diabetes and Endocrinology Unit, Assaf Harofeh Medical Center Zerifin affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Zerifin 70300, Israel. mrapoport@asaf.health.gov.il
authors.forename: Micha J
authors.initials: MJ
authors.lastname: Rapoport
authors.forename: Tzvi
authors.initials: T
authors.lastname: Bistritzer
authors.forename: Dorit
authors.initials: D
authors.lastname: Aharoni
authors.forename: Mordechai
authors.initials: M
authors.lastname: Weiss
authors.forename: Yoram
authors.initials: Y
authors.lastname: Ramot
authors.forename: Andreas
authors.initials: A
authors.lastname: Buchs
authors.forename: Konstantin
authors.initials: K
authors.lastname: Bloch
authors.forename: Pnina
authors.initials: P
authors.lastname: Vardi
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D013997:Time Factors
chemical_list: D016207:Cytokines