Endocrine Abstracts

Many endocrine disorders bear an immunological component and involve local cytokines as paracrine signals. Moreover, certain auto-antibodies appear as causative pathological agents in some of the most common endocrine diseases e.g. in type I diabetes mellitus or different forms of autoimmune thyroid disease (AITD). Recently, selenium (Se) status and selenoproteins have emerged as important modifiers of the inflammatory response, AITD or sepsis. Notably, mortality risk of patients with severe sepsis appeared negatively correlated to serum Se concentrations and prognosis improve upon Se supplementation in a recent multicentric trial. In an attempt to study the importance of the Se status for inflammation-dependent pathologies, we subjected mice on different Se supply to an LPS-induced acute phase response. First, we tested whether the acute phase induced alterations affect preferentially the essential trace element Se or rather represent a more general impairment of the hepatic trace element metabolism. Among all these trace elements tested (including Fe, Cu, and Zn), only Se showed a very pronounced decline during the acute phase response. Next, we analyzed the importance of the baseline Se status for the response. Se-concentrations in serum and liver declined to approx. 50% of control values 24 h after LPS injection in a Se-supplemented group, whereas Se-poor animals maintained a constant value at a low baseline. More importantly, cytokine production was strongly affected by the Se-status. The Se poor animals displayed significantly augmented concentrations of the circulating cytokines IL6 (P≤0.05) and MCP1 (P≤0.01) compared to the Se-supplemented mice. This effect was especially pronounced in the male mice and pointed to certain sex-specific differences. We conclude that Se-based adjuvant supplementation efforts might improve selenoprotein expression and immune function during inflammation avoiding an exaggerated induction of pro-inflammatory cytokines. This mechanism might underlie the positive Se supplementation results which have been observed in recent AITD trials. Further studies are needed to test which patients are in need of Se supplementation and how their inflammatory response or autoimmune antibody load respond to an improved Se supply.