Interleukin-12 (IL-12) is a heterodimeric cytokine produced by macrophages and dendritic cells that has a central role in cell-mediated immune responses through its ability to polarize T helper (Th)0 lymphocytes into the Th1 subset by stimulating interferon gamma (IFN-␥) production by the T lymphocytes and natural killer cells. 1 Dysregulated production of IL-12 is thought to be pathogenically involved in the development of Th1-dependent immunoinflammatory diseases such as insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, autoimmune thyroiditis, Crohn's disease, and multiple sclerosis (reviewed in Trembleau et al. 2 ). Hence, studies conducted by ourselves and others in rodent models of these diseases show that blockade of endogenous IL-12 with specific antagonists such as neutralizing, monoclonal antibody (mAb) to IL-12 or the IL-12p40 homodimer ameliorates the course of the diseases. 3-9 Conversely, exogenous IL-12 accelerates the onset and increases the incidence of IDDM in NOD mice and augments the severity of the other disease models. 8,[10][11][12] Under certain conditions, however, IL-12 has had beneficial effects in mice suffering from Th1-mediated autoimmune diseases. 8,[13][14][15][16] This is thought to be mediated by the ability of IL-12 to stimulate the production of Th2-derived anti-inflammatory cytokines such as IL-4 and IL-10 17-20 (reviewed in Muraille and Leo 21 ).Few and contradictory results have also been obtained regarding the role of IL-12 in immunoinflammatory hepatitis. Although IL-12 does not induce liver damage by itself, 22 its synthesis is up-regulated in vivo in murine hepatitis virus infection, 23 and IL-12 induces a cytolytic response against regenerating hepatocytes primarily through its enhancement of tumor necrosis factor (TNF) production. 24 Using a model of hepatitis that can be induced in Propionibacterium acnesprimed mice by low doses of lipopolysaccharide (LPS), Tanaka et al. 25 observed that anti-IL-12 mAb given after challenge with P. acnes protected the mice from the hepatitisinducing effect of LPS. Conversely, exogenous IL-12 rendered otherwise resistant BALB/c mice susceptible to P. acnes/LPSinduced hepatitis. 25 Recently, Tsutsui et al. 26 found that anti-IL-18 mAb, but not anti-IL-12 mAb prevented P. acnes/LPSinduced hepatitis when these antibodies were injected immediately before LPS challenge. 26 Hepatitis can also be induced in mice given a single intravenous injection of 20 mg/kg of Concanavalin A (ConA) 27,28 (reviewed in Lohse and Meyer zum Bushenfelde 29 ). This disease is characterized by a markedly increased plasma level of alanine transaminase (ALT) 8 to 24 hours after injection and simultaneous infiltration of the liver with neutrophils, macrophages, and T cells, followed by apoptosis and necrosis of the hepatocytes. [27][28][29] The contribution of T cells in this model is underscored by the resistance of nude athymic mice to the hepatitis-inducing effect of ConA and by the preventive effect

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Introduction: Standardized methods of reporting complications after radical cystectomy (RC) and urinary diversions (UD) are necessary to evaluate the morbidity associated with this operation to evaluate the modified Clavien classification system (CCS) in grading perioperative complications of RC and UD in a real life cohort of patients with bladder cancer. Materials and methods: A consecutive series of patients treated with RC and UD from April 2011 to March 2012 at 19 centers in Italy was evaluated. Complications were recorded according to the modified CCS. Results were presented as complication rates per grade. Univariate and binary logistic regression analysis were used for statistical analysis. Results: Results and limitations: 467 patients were enrolled. Median age was 70 years (range 35e89). UD consisted in orthotopic neobladder in 112 patients, ileal conduit in 217 patients and cutaneous ureterostomy in 138 patients. 415 complications were observed in 302 patients and were classified as Clavien type I (109 patients) or II (220 patients); Clavien type IIIa (45 patients), IIIb (22 patients); IV (11 patients) and V (8 patients). Patients with cutaneous ureterostomy presented a lower rate (8%) of CCS type IIIa ( p ¼ 0.03). A longer operative time was an independent risk factor of CCS III (OR: 1.005; CI: 1.002e1.007 per minute; p ¼ 0.0001).

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