Interleukin 32 (IL-32) is a recently described proinflammatory cytokine that activates p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-jB), thereby inducing proinflammatory cytokines such as IL-1b and tumor necrosis factor alpha (TNFa). We investigated the role of IL-32 in patients with chronic hepatitis C virus (HCV) infection. Steady-state hepatic messenger RNA (mRNA) levels of IL-32 were determined in a cohort of 90 subjects; anti-IL-32 staining was used in a second cohort of 132 consecutive untreated chronic HCV patients. Correlations with histological features of steatosis, inflammation, and fibrosis were made. In vitro, endogenous IL-32 in monocytes and in the human hepatoma cell line Huh-7.5 were examined. The effects of IL-32-overexpression and IL-32-silencing on HCV replication were studied using HCV luciferase reporter viruses. There were highly significant positive associations between hepatic IL-32 mRNA expression and liver steatosis, inflammation, fibrosis, smooth muscle actin (SMA) area, and serum alanine aminotransferase (ALT) levels. IL-32 protein expression was positively associated with portal inflammation, SMA area, and ALT. In vitro, IL-1b and TNF-a significantly induced IL-32 expression in human Huh-7.5 cells. Alone, stimulation with interferon alpha (IFN-a) did not induce IL-32 expression in Huh-7.5. However, IFN-a exerted a significant additive effect on TNF-a-induced but not IL-1b-induced IL-32 expression, particularly in CD14 1 monocytes. This effect was dependent both on NF-jB and Jak/STAT signaling. Viral infection of Huh-7.5 cells resulted in a significant (11-fold) induction of IL-32 mRNA expression. However, modulation of IL-32 in Huh-7.5 cells by overexpression or silencing did not influence HCV virus replication as determined by luciferase assays. Conclusion: IL-32 is a novel proinflammatory cytokine involved in HCV-associated liver inflammation/fibrosis. IL-32 is expressed by human hepatocytes and hepatoma cells and its expression is regulated by proinflammatory stimuli.

BackgroundWorksite health promotion (WHP) initiatives are increasingly seen as having potential for large-scale health gains. While health insurance premiums are directly linked to workplaces in the USA, other countries with universal health coverage, have less incentive to implement WHP programs. Size of the business is an important consideration with small worksites less likely to implement WHP programs. The aim of this study was to identify key intervention points and to provide policy makers with evidence for targeted interventions.MethodsThe worksites (n = 218) of randomly selected, working participants, aged between 30 and 65 years, in two South Australian cohort studies were surveyed to assess the practices, beliefs, and attitudes regarding WHP. A survey was sent electronically or by mail to management within each business.ResultsSmaller businesses (<20 employees) had less current health promotion activies (mean 1.0) compared to medium size businesses (20–200 employees – mean 2.4) and large businesses (200+ employees – mean 2.9). Management in small businesses were less likely (31.0 %) to believe that health promotion belonged in the workplace (compared to 55.7 % of medium businesses and 73.9 % of large businesses) although half of small businesses did not know or were undecided (compared to 36.4 and 21.6 % of medium and large businesses). In total, 85.0 % of smaller businesses believed the health promotion activities currently employed in the worksite were effective (compared to 89.2 % of medium businesses and 83.1 % of large businesses). Time and funding were the most cited responses to the challenges to implementing health promoting strategies regardless of business size. Small businesses ranked morale and work/life balance the highest among a range of health promotion activities that were important for their workplace while work-related injury was the highest ranked consideration for large businesses.ConclusionThis study found that smaller workplaces had many barriers, beliefs and challenges regarding WHP. Often small businesses find health promotion activities a luxury and not a serious focus of their activities although this study found that once a health promoting strategy was employed, the perceived effectiveness of the activities were high for all business regardless of size. Tailored low-cost programs, tax incentives, re-orientation of work practices and management support are required so that the proportion of small businesses that have WHP initiatives is increased.

Obesity and fatty liver are commonly observed among patients with chronic hepatitis C virus (HCV) and are risk factors for increased hepatic fibrosis. Obesity is accompanied by a low-grade, chronic inflammatory response that may contribute to pathogenesis of obesityrelated comorbidities. To assess whether obesity and steatosis potentiate expression of inflammatory markers in chronic HCV, serum protein and hepatic messenger RNA (mRNA) levels of c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-␣) were measured in 171 patients with chronic HCV. The relationships of body mass index, steatosis, histological features of inflammation and fibrosis with serum and hepatic levels of these factors were determined. In comparison with lean patients, overweight and obese subjects had increased circulating (P < 0.001) and hepatic (P ‫؍‬ 0.003) CRP, and there was a significant correlation between serum protein and hepatic CRP mRNA levels (r s ‫؍‬ 0.51, P < 0.001). Obesity (P ‫؍‬ 0.001) and steatosis (P < 0.001) were associated with increased circulating but not hepatic IL-6, and a weak correlation was seen between serum protein and hepatic IL-6 mRNA levels (r s ‫؍‬ 0.29, P ‫؍‬ 0.003). An independent relationship was seen between hepatic TNF-␣ mRNA levels and higher total inflammatory score (P < 0.001) and stage of fibrosis (P ‫؍‬ 0.037). Subjects with HCV genotype 3 had lower hepatic TNF-␣ mRNA levels compared with subjects with genotype 1 (P ‫؍‬ 0.017), but there was no relationship between serum TNF-␣ protein and hepatic TNF-␣ mRNA levels. Conclusion: In patients with chronic HCV, obesity and steatosis are associated with increased expression of selected inflammatory markers; however, circulating levels of IL-6 and TNF-␣ do not reflect hepatic expression. Hepatic TNF-␣ was associated with both increased inflammatory activity and hepatic fibrosis, providing support for the key role of this pro-inflammatory cytokine in liver injury in chronic HCV. (HEPATOLOGY 2008;48:80-87.)