The role of leptin was investigated in two models of T cell-mediated hepatitis: the administration of Con A or of Pseudomonas aeruginosa exotoxin A (PEA). In both models, leptin-deficient (ob͞ob) mice were protected from liver damage and showed lower induction of tumor necrosis factor (TNF) ␣ and IL-18 compared with their lean littermates. Neutralization of TNF-␣ reduced induction of IL-18 by either Con A (70% reduction) or PEA (40% reduction). Pretreatment of lean mice with either soluble TNF receptors or with an anti-IL-18 antiserum significantly reduced Con A-and PEA-induced liver damage. The simultaneous neutralization of TNF-␣ and IL-18 fully protected the mice against liver toxicity. However, neutralization of either IL-18 or TNF-␣ did not inhibit Con A-induced production of IFN-␥. Thymus atrophy and alterations in the number of circulating lymphocytes and monocytes were observed in ob͞ob mice. Exogenous leptin replacement restored the responsiveness of ob͞ob mice to Con A and normalized their lymphocyte and monocyte populations. These results demonstrate that leptin deficiency leads to reduced production of TNF-␣ and IL-18 associated with reduced T cell-mediated hepatotoxicity. In addition, both TNF-␣ and IL-18 appear to be essential mediators of T cell-mediated liver injury.

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and Nikos Solounias (Fortelius & Solounias 2000), right up to his most recent collaborations (Kaiser et al. 2013). Offered in honour of Mikael's career, our current paper builds on an effort to model dental wear processes at the nanoscale (Lucas et al. 2013), attempting in some small way to emulate Mikael's ingenuity in offering new dimensions to the subject.