1Mabrouk Ghonaim, 2Rawhia El-Edel, 3Nabil El-Kafrawi and Aly Abdel Rheim
Departments of 1Microbiology and Immunology, 2Clinical pathology and 3Internal Medicine Faculty of Medicine, Menoufiya and Alexandria Universities.
The pathogenesis of type 1 (insulin-dependent) diabetes
mellitus (IDDM) is believed to result from a defective pattern of cytokine
secretion. Cytokines released by macrophages/monocytes and T lymphocytes may
have an initial role in b-cell
damage. The aim of this study was to estimate serum IL-12 and IFN-g
levels and to assess their in vitro production by peripheral blood
mononuclear cells (PBMCs) from high-risk first degree relatives of type 1
diabetic patients and from recently diagnosed IDDM patients. The study included
12 patients with recent-onset IDDM, 24 high-risk relatives and 10 healthy
controls. Whole blood cell cultures were done in the presence of
phytohaemagglutinin (PHA) for 48 hours. IL-12 and IFN-g were measured in the culture
supernates and sera using enzyme immunoassay. Results showed significantly
higher serum IL-12 levels in IDDM patients (p< 0.01) and high-risk relatives
(p< 0.001) and serum IFN-g
levels in patients (p< 0.001 ) and high-risk relatives (p< 0.01) as
compared to that of the controls. There was significantly (p< 0.01) higher
levels of IFN-g in
culture supernates obtained from patients and high-risk relatives than that of
the controls. However, the levels of IL-12 in culture supernates were
non-significantly higher in both patients and relatives when compared to that
of the controls. In conclusion, IL-12 is overproduced in the prediabetic phase
leading to a shift in T helper cells toward Th1 type, culminating in increased
production of IFN-g
which may lead to insulitis and b-cell
destruction and diabetes. Neutralization of this effect in high-risk relatives
may prevent the development of the disease.