Hepatitis C Virus Infection of Cultured Human Hepatoma Cells Causes Apoptosis and Pyroptosis in Both Infected and Bystander Cells.

Individuals infected with hepatitis C virus (HCV) are at high risk of developing progressive liver disease, including cirrhosis and hepatocellular carcinoma (HCC). How HCV infection causes liver destruction has been of significant interest for many years, and apoptosis has been proposed as one operative mechanism. In this study, we employed a tissue culture-adapted strain of HCV (JFH1T) to test effects of HCV infection on induction of programmed cell death (PCD) in Huh-7.5 cells. We found that HCV infection reduced the proliferation rate and induced caspase-3-mediated apoptosis in the infected cell population. However, in addition to apoptosis, we also observed infected cells undergoing caspase-1-mediated pyroptosis, which was induced by NLRP3 inflammasome activation. By co-culturing HCV-infected Huh-7.5 cells with an HCV-non-permissive cell line, we also demonstrated induction of both apoptosis and pyroptosis in uninfected cells. Bystander apoptosis, but not bystander pyroptosis, required cell-cell contact between infected and bystander cells. In summary, these findings provide new information on mechanisms of cell death in response to HCV infection. The observation that both apoptosis and pyroptosis can be induced in bystander cells extends our understanding of HCV-induced pathogenesis in the liver.

Diagnostic markers for neonatal sepsis: comparing C-reactive protein, interleukin-6 and immunoglobulin M.

This clinical study was conducted to evaluate the diagnostic value of C-reactive protein (CRP), interlekin-6 (IL-6) and immunoglobulin M (IgM) in the early diagnosis of neonatal sepsis. The diagnostic values of each marker separately or in combinations were evaluated. The optimal cut-off values of each marker in the diagnosis of neonatal sepsis were defined. Between December 2004 and March 2005, a total of 78 neonates at different ages with different diagnoses in a neonatal intensive care unit in North Jordan were enrolled. Patients were classified into 'sepsis' group, 'probable sepsis' group and 'no sepsis' group. Blood samples were collected for CRP, IL-6 and IgM determination. A CRP value of 5 mg/l was the best among the three parameters with 95% sensitivity and 98% negative predictive value. Combination between parameters was helpful in enhancing the ability to diagnose sepsis. The best combination was CRP > or = 5 mg/l and/or IgM of > or =20 mg/dl. We conclude that CRP, IL-6 and IgM are helpful in the early diagnosis of Gram-negative neonatal sepsis. However, CRP continues to be the best single test. The use of both CRP and IgM in combination was the most helpful in predicting Gram-negative neonatal sepsis. We speculate a significant role of this combination in making decisions regarding antibiotics treatment and upgrading the level of medical care and observation in a setting where Gram-negative micro-organisms are causing the majority of neonatal infections.