The relative balance between Th1 and Th2 cytokines appears crucial, since the role of cytokines has been evaluated in several studies by comparison of clinically heterogeneous groups of patients. The aim of this study is to determine the role of proinflammatory Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-␥), and anti-inflammatory Th2 cytokines, IL-4 and IL-10, in a homogeneous group of patients with uncomplicated Plasmodium falciparum malaria. Levels of IL-12, IFN-␥, Il-4, and IL-10 in serum for 20 adult patients and 15 healthy control subjects were determined by an immunoenzymatic assay. Serum levels of Th1 cytokines, IL-12 (8.6 ؎ 2.8 pg/ml; controls, 3.2 ؎ 0.7 pg/ml) and IFN-␥ (39.2 ؎ 67.6 pg/ml; controls, 8.4 ؎ 6.3 pg/ml), were significantly increased at admission; 3 days later, levels of IL-12 in serum remained significantly high (8.8 ؎ 2.6 pg/ml), whereas IFN-␥ levels returned to control values. The anti-inflammatory response of Th2 cytokines (IL-10 and IL-4) was distinct. Levels of IL-10 in serum were not significantly increased at day 0 and day 3 (306.6 ؎ 200.4 pg/ml and 56.6 ؎ 38.4 pg/ml, respectively; controls, 17.4 ؎ 9.0 pg/ml). In contrast, levels of IL-4 in serum were not increased on admission (3.4 ؎ 1.2 pg/ml; controls, 2.4 ؎ 0.8 pg/ml), but at day 3 a moderate and significant increase of IL-4 levels was observed (4.5 ؎ 1.7 pg/ml). In conclusion, the increase of Th1 cytokine IL-12 and IFN-␥ levels during the acute phase of uncomplicated P. falciparum malaria may reflect an early and effective immune response regulated by proinflammatory Th1 cytokines, and in particular IFN-␥ may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.

Serum levels of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in patients with acute viral hepatitis were investigated. Twelve patients suffering from acute viral hepatitis were studied; 8 patients presented with acute hepatitis B, 2 patients with acute hepatitis A, and 2 patients with acute hepatitis C. Serum levels of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were significantly increased in all patients with acute viral hepatitis. Decreased serum levels of all cytokines were noted in four patients with acute hepatitis B during the recovery phase of infection. In addition, IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were undetectable at the end of a follow-up period of 6 months. Our study shows that increased levels of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha are probably related to hepatitis activity and thus may have some role in hepatocytic injury.

A meta-analysis of six randomized clinical trials involving 240 children with chronic hepatitis B treated with recombinant interferon-alpha (IFN-alpha) was performed. IFN-alpha treatment was effective in blocking viral replication. Clearance of hepatitis B virus (HBV) DNA from sera occurred in 44 of 127 treated patients (P < .00001), and clearance of hepatitis B e antigen (HBeAg) occurred in seven of 74 treated patients (P = .099). IFN-alpha normalized serum levels of alanine aminotransferase (ALT) in 33 of 85 treated patients (P = .017). At the end of the follow-up period, viral replication was still reduced in IFN-alpha-treated patients, HBV DNA clearance occurred in 36 of 126 patients (P = .014), and HBeAg clearance occurred in 29 of 126 patients (P = .026). Regarding these virological and biochemical endpoints, we found that prolonged therapy (> 6 months) was associated with a better response, whereas high dosages of IFN-alpha were not. These findings could be biased by limited follow-up. Children with high ALT levels had a better response. However, these randomized clinical trials had some methodological flaws, including the lack of information on histologic response to IFN-alpha treatment by pediatric patients and the absence of "hard outcomes" (such as survival or development of cirrhosis or hepatocellular carcinoma).

A retrospective analysis of data from a cohort of patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were treated with highly active antiretroviral therapy (HAART) at 3 infectious diseases units in northern Italy was performed. While the patients were receiving HAART, CD4(+) cell counts significantly increased and HIV RNA serum levels decreased. However, no significant overall changes in alanine aminotransferase (ALT) levels and HCV RNA serum levels were observed. Fifteen (4.6%) of 323 patients died within 3 years of follow-up; death was related to cirrhosis in 5 patients (1.6%). No significant difference was observed between cirrhosis-related mortality and mortality related to other causes. Patients with ALT levels >4 times the normal values at initiation of HAART showed a significant decrease in ALT levels, whereas patients with normal ALT levels at initiation of HAART showed a significant increase over time, suggesting that HAART may have long-term beneficial or detrimental effects, depending on patient characteristics.

The systemic inflammatory response syndrome (SIRS) is an inflammatory process seen in association with a large number of clinical infective and non-infective conditions. The aim of this study was to investigate the role of anti-inflammatory cytokines such as interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta). Serum levels of IL-4, IL-10 and TGF-beta were determined in 45 patients with SIRS: 38 patients had SIRS of infectious origin, whereas seven patients had non-infectious SIRS. Twenty healthy subjects were used as controls. Serum levels of IL-4, IL-10 and TGF-beta were determined by an immunoenzyme assay. A significant increase of IL-4 was observed in these patients at the time of diagnosis and 5 days later. In contrast, serum levels of IL-10 were not increased at the time of diagnosis, but a slight decrease was noted after 5 days. Serum levels of TGF-beta were not increased at time of diagnosis, and a slight increase was observed after 5 days. Serum levels of IL-4 were significantly higher in patients with infectious SIRS at the time of diagnosis, whereas no significant difference between infectious and non-infectious SIRS was noted for serum levels of IL-10 and TGF-beta at the time of diagnosis and 5 days later. During SIRS, serum levels of IL-4 were significantly increased with a significant correlation between IL-4 and mortality, and only levels of IL-4 were significantly increased in the SIRS caused by infectious stimuli.