Interleukin-15 Plays a Central Role in Human Kidney Physiology and Cancer through the γc Signaling Pathway

The ability of Interleukin-15 (IL-15) to activate many immune antitumor mechanisms renders the cytokine a good candidate for the therapy of solid tumors, particularly renal cell carcinoma. Although IL-15 is being currently used in clinical trials, the function of the cytokine on kidney's components has not been extensively studied; we thus investigated the role of IL-15 on normal and tumor renal epithelial cells. Herein, we analyzed the expression and the biological functions of IL-15 in normal renal proximal tubuli (RPTEC) and in their neoplastic counterparts, the renal clear cell carcinomas (RCC). This study shows that RPTEC express a functional heterotrimeric IL-15Rαβγc complex whose stimulation with physiologic concentrations of rhIL-15 is sufficient to inhibit epithelial mesenchymal transition (EMT) commitment preserving E-cadherin expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but it can also preserve the renal epithelial phenotype through the γc-signaling pathway, demonstrating that the cytokine possess a wide range of action in epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a defect in the expression of γc-receptor and JAK3 associated kinase, which strongly impacts IL-15 signaling. Indeed, in the absence of the γc/JAK3 couple we demonstrate the assembly of an unprecedented functional high affinity IL-15Rαβ heterodimer, that in response to physiologic concentrations of IL-15, triggers an unbalanced signal causing the down-regulation of the tumor suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of IL-15/γc-dependent signaling (STAT5), by co-transfecting γc and JAK3 in RCC, inhibits EMT reversion. In conclusion, these data highlight the central role of IL-15 and γc-receptor signaling in renal homeostasis through the control of E-cadherin expression and preservation of epithelial phenotype both in RPTEC (up-regulation) and RCC (down-regulation)

CLINIMETRIC ASSESSMENT OF PSYCHOLOGICAL AND PSYCHOSOCIAL FACTORS OF MIGRAINE: A PILOT STUDY

Introduction: migraine has widely been associated with an increased prevalence of psychosocial and mental health difficulties. Objectives: the aim of this pilot study is to assess well-being, distress, disability, perception and beliefs about the state of health and illness, in a group of patients with migraine without aura. Contextually it considers if there are significant differences between patients with episodic migraine and chronic migraine. Methods: a sample of 30 outpatients (15 with episodic migraine, 15 with chronic migraine) underwent the following interviewer-based and self-rated psychometric evaluation: Structured Clinical Interview for DSM Disorder (SCID; First at al., 1994), Interview for the Diagnostic Criteria for Psychosomatic Research (DCPR; Porcelli & Sonino, 2007), Psychosocial Index (PSI; Sonino & Fava, 1998), Migraine Disability Assessment (MIDAS; Stewart et al., 2001), Symptom Questionnaire (SQ; Fava et al., 1983; Kellner, 1987), Psychological Well-Being Scale (PWB; Ryff, 1989), Brief Illness Perception Questionnaire (B-IPQ; Broadbent et al., 2006) and Illness Behaviour Questionnaire (IBQ; Pilowsky &Spence 1975; Fava et al., 1982). Pearson\u2019s coefficient was used to analyze correlations between psychological and psychosocial variables. Results: chronic migraine patients showed significantly higher levels of migraine disability (MIDAS) (p=0.03), a worse illness perception (B-IPQ) (p=0.00) and higher scores in psychological/somatic perception of illness (IBQ) (p=0.05) compared to episodic migraine patients. Moreover, the majority of patients considers the psychological problems as the main causal factor of their illness, meets the criteria of allostatic load and reports a high prevalence of the DCPR syndromes. The correlations between index of disability, perception of illness, abnormal illness behavior and some psychosomatic syndromes were positive and significant. Conclusions: the results confirm the need to assess migraine within the biopsychosocial model

Oral versus short-term intratympanic prednisolone therapy for idiopathic sudden hearing loss

Objectives: To assess the therapeutic effectiveness of an intratympanic (IT) steroid protocol compared to a systemic steroid protocol. Methods: A total of 265 consecutive patients presenting unilateral idiopathic sudden sensorineural hearing loss were divided into 2 groups. One group comprised 131 patients enrolled between May 2009 and May 2010, and the other consisted of 134 patients enrolled between June 2010 and June 2011; a total of 48 patients were excluded among the 2 groups. The first group received oral prednisone for 8 days in tapering doses; the second group had IT prednisolone at a dose of 62.5 mg/ml once a day for 3 consecutive days. Audiological examinations were performed at study entry and 30 days after the beginning of therapy. Mean pure tone audiometry (PTA) of both groups and hearing outcomes following the criteria of Furuhashi et al. [Clin Otolaryngol 2002; 27: 458-463] and Siegel [Otolaryngol Clin North Am 1975; 8: 467-473] were investigated. Results: The strong efficacy of steroid therapy was evident in both groups, observing both PTA and hearing threshold improvement. The evaluation of the hearing outcomes shows a significantly better result for the short-term IT protocol; this result is ascribable to two types of audiometric curves: down-and up-sloping. Conclusion: The results show a significant efficacy of both steroid therapeutic approaches. There was no significant difference in PTA improvement between the 2 study groups; the short-term IT protocol led to better results in the evaluation of the hearing outcomes (following the criteria of Siegel and Furuhashi et al.) for up-and down-sloping audiometric curves