Macrophages and dendritic cells infiltrating islets with or without beta cells produce tumour necrosis factor-alpha in patients with recent-onset type 1 diabetes.
OBJECTIVE
Type 1A diabetes results from autoimmune destruction of pancreatic beta cells. We examined the involvement of TNF-alpha and IL-1beta, as well as of T cells, macrophages and dendritic cells, in the destruction of beta cells in patients with recent-onset type 1 diabetes.


METHODS
We obtained pancreatic biopsy specimens from six patients with recent-onset type 1 diabetes and analysed these by immunohistochemistry.


RESULTS
T cell infiltration was less common in islets without beta cells (12.5 [0-33.3]%) than in those with beta cells (46.0 [17.4-83.3]%), while macrophages and dendritic cells showed a similar extent of infiltration into islets both with or without beta cells. TNF-alpha was detected in 25.0 (4.3-46.9)% of macrophages and 11.8 (0-40.0)% of dendritic cells infiltrating the islets in samples from each patient, but not at all in T cells. IL-1beta was detected in 1.8 (0-11.3)% of T cells infiltrating the islets with beta cells, while it was found in 19.2 (0-35.3)% of macrophages or 10.7 (0-31.3)% of dendritic cells infiltrating the islets in samples from each patient (all values median [range]).


CONCLUSIONS
Macrophages and dendritic cells infiltrate the islets and produce inflammatory cytokines (TNF-alpha and IL-1beta) during the development of type 1A diabetes.
Uno
S
S
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, and Department of Internal Medicine, Mino City Hospital, Japan.
Imagawa
A
A
Okita
K
K
Sayama
K
K
Moriwaki
M
M
Iwahashi
H
H
Yamagata
K
K
Tamura
S
S
Matsuzawa
Y
Y
Hanafusa
T
T
Miyagawa
J
J
Shimomura
I
I
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D003713:Dendritic Cells / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology; D007515:Islets of Langerhans / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood
D015703:Antigens, CD; D014409:Tumor Necrosis Factor-alpha