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Cytokine production in NOD mice on prophylactic insulin therapy
Author(s) -
STRANDELL EVA,
KAAS ANNE,
HARTOFTNIELSEN MARIELOUISE,
BOCK TROELS,
BUSCHARD KARSTEN,
BENDTZEN KLAUS
Publication year - 1999
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1699-0463.1999.tb01574.x
Subject(s) - nod , cytokine , medicine , nod mice , insulin , immunology , diabetes mellitus , endocrinology
We investigated whether cytokines produced primarily by monocytes/macrophages (IL‐1α), Th1‐lymphocytes (IFNγ), or Th2‐lymphocytes (IL‐4) are modulated in diabetes‐prone NOD mice by insulin treatment as used in prophylaxis studies. The cytokines were measured by ELISA in plasma and in supernatants of spleen cells activated ex vivo by lipopolysaccharide plus phytohemagglutinin. Insulin, 0.25–0.50 IU/day, was given subcutaneously for 8 weeks starting in 4‐week‐old female mice. The insulin‐treated and control NOD mice showed similar weight gains and, by the end of the study, both groups exhibited cell infiltration in about 25% of their islets. IL‐la, IFNγ and IL‐4 were generally below detection in plasma of prediabetic animals and controls. Diabetic NOD mice, aged 28–45 weeks, had significantly elevated plasma IL‐la: 154±39 pg/ml (mean±M, p<0.0001). While ex vivo activated NOD splenocytes released similar amounts of IL‐1α, insulin therapy increased the levels from 99±17 to 155±19 pg/10 6 cells (p<0.05). Supernatants of activated splenocytes from prediabetic NOD mice had lower levels of IL‐4 (<15 pg/10 6 cells) compared with those from BALB/c mice (88±22 pg/10 6 cells; p<0.01), and this deficiency was partially compensated for when the NOD mice were given insulin (27±8; p<0.01). The levels of IFNγ were comparable and largely unaffected by insulin treatment. Hence, insulin therapy appears to partially normalize an otherwise deficient Th2 response in NOD mice.