DIFFERENTIAL PATTERNS OF PRODUCTION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, IL-2, IL-3 AND IL-4 BY CULTURED ISLETS OF LANGERHANS FROM NONOBESE DIABETIC AND NONDIABETIC STRAINS OF MICE

A Terasaki plate microculture system was developed to examine cytokine secretion by cultured islets of Langerhans from non-obese diabetic (NOD) and non-diabetic strains of mice. NOD islets were also scored for the degree of infiltrating mononuclear cell release after overnight culture to see if this correlated with cytokine levels. Each of the cytokines studied, i.e. granulocyte-monocyte colony stimulating factor (GM-CSF), IL-2, IL-3 and IL-4, showed different patterns of production. For NOD islets, GM-CSF and IL-3 levels correlated with the degree of infiltrate release, although production was not confined to islets that released mononuclear cells in vitro. However, GM-CSF differed from IL-3 in that it was produced by islets from some non-diabetic strains of mice, whereas IL-3 production was confined to NOD islets. Surprisingly little IL-2 could be detected in NOD islet supernatants and message for IL-2 was not detected by reverse transcription polymerase chain reaction. Finally, male NOD islets produced more IL-4 than females, possibly related to the lower incidence of diabetes in males, but unlike GM-CSF and IL-3, IL-4 production did not correlate with the degree of infiltrate released in culture. Overall the results show a complicated pattern of cytokine production that may be associated with destructive or protective responses. This was particularly illustrated by the fact that islet production of all cytokines temporarily ceased in male NOD mice between 6 and 10 weeks of age, a phenomenon not seen in females.