Induction of interferon-gamma and IL-4 production by mitogen and specific antigens in peripheral blood lymphocytes of Type 1 diabetes patients.
A functional imbalance in cytokine production resulting in dominance of Th1 over Th2 type response has been suggested to play a critical role in the pathogenesis of type 1 diabetes. In this study the cellular responses to pokeweed mitogen and a panel of specific antigens were analysed by measuring the production of IFN-gamma and IL-4 cytokines at the levels of mRNA expression (expression index=antigen/medium) and protein secretion in culture supernatants. Two enterovirus preparates were included due to the suggested significance of these viruses in the aetiology of type 1 diabetes. The study included 22 children with newly-diagnosed type 1 diabetes, 15 children with longer duration of disease and 20 healthy children. Comparisons were made between age- and sex-matched groups. Newly diagnosed diabetic patients had significantly higher IFN-gamma mRNA expression index (p<0.02) but also higher IL-4 mRNA expression index (p<0.05) in tetanus toxoid stimulated peripheral blood mononuclear cells compared to healthy controls. Also the diabetic patients studied 3-72 months after the diagnosis of type 1 diabetes showed a tendency to higher IFN-gamma mRNA expression index compared to controls (0.05<p<0.1). Enhanced mitogen-stimulated IFN-gamma mRNA expression index was observed in children with newly-diagnosed type 1 diabetes when compared to subjects with longer duration of diabetes (p<0.05). No significant differences were observed in IFN-gamma produced into the culture supernatants. In conclusion, imbalance in both IFN-gamma and IL-4 mRNA levels was demonstrated between diabetic patients and healthy subjects.
Halminen
M
M
JDFI Centre for Prevention of Type 1 Diabetes, Finland.
Juhela
S
S
Vaarala
O
O
Simell
O
O
Ilonen
J
J
D000293:Adolescent; D000941:Antigens / Q000008:administration & dosage; D000956:Antigens, Viral / Q000008:administration & dosage; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D029822:Enterovirus B, Human / Q000276:immunology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D011043:Pokeweed Mitogens / Q000494:pharmacology; D017955:Poliovirus / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013745:Tetanus Toxoid / Q000008:administration & dosage; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014373:Tuberculin / Q000008:administration & dosage
D000941:Antigens; D000956:Antigens, Viral; D011043:Pokeweed Mitogens; D012333:RNA, Messenger; D013745:Tetanus Toxoid; D014373:Tuberculin; D015847:Interleukin-4; D007371:Interferon-gamma