CYTOKINE OVERPRODUCTION IN HEALTHY FIRST DEGREE RELATIVES OF PATIENTSWITH IDDM

Healthy family members of patients with insulin-dependent diabetes mel litus (IDDM) are known to share a number of immunological abnormalitie s with their affected relatives. Since monocyte and type 1 T-cell-deri ved cytokines contribute to the pathogenesis of IDDM, we studied the p roduction of these cytokines in the healthy first degree relatives of 29 children with IDDM. We report that circulating tumour necrosis fact or-alpha (TNF-alpha) and soluble interleukin-2 (sIL-2) receptor were p resent in increased amounts in non-diabetic family members at levels s imilar to those found in the diabetic children (duration of disease 3 months - 5 years). Furthermore, marked hypersecretion of IL-1 alpha an d TNF-alpha by mitogen-stimmulated peripheral blood mononuclear cells was found in both diabetic and healthy family members. Abnormalities o f cytokine production in healthy relatives did not correlate with the presence of islet cell antibodies or with HLA DR type. These data indi cate that healthy family members of patients with IDDM exhibit overpro duction of a number of cytokines that have been implicated in diabetog enesis.