IL-4 and reactive oxygen species are elevated in Egyptian patients affected with schistosomal liver disease.
Schistosomiasis is a chronic liver disease that is endemic in rural areas of Egypt. Some patients may acquire infection and develop minimal complications while others may develop severe complications and progress to portal hypertension and cirrhosis especially if co-infected with hepatitis C virus (HCV). The reasons for this are poorly understood. Previous studies suggested an independent role for Th2-biased cytokine responses to schistosomal antigens in persistent hepatic fibrosis and development of complications. Studies in murine schistosomiasis demonstrated that the development of fibrosis requires the production of the profibrotic cytokines such as IL-4. On the other hand, previous studies have suggested that reactive oxygen species may play an important role in schistosomal granuloma formation and disease progression


OBJECTIVE
To investigate the status of the profibrotic IL-4 cytokine, oxidative stress (as indicated by thiobarbituric acid reactive substances), the antioxidants enzymes catalase and red blood cells glutathione content in a cohort of Egyptian patients affected with schistosomal hepatic disease and or hepatitis C infection.


METHODS
The current study included four groups: patients with isolated HCV infection (HCV), comprised of 22 patients aged (mean +/- SD) 51.3 +/- 4.7 years; patients with HCV and schistosomal hepatic fibrosis (SHF) (Co-infected patients), comprised of 22 patients aged 49.6 +/- 4.0 years, patients with pure chronic schistosomiasis comprised of 22 patients with chronic schistosomiasis aged 53.7 +/- 5.6 years and a control group, comprised of 22 control subjects aged 48.5 +/- 5.4 years. Thiobarbituric acid reactive substances (TBARS), Catalase activity and red blood cells glutathione contents were determined using chemical methods while plasma IL-4 was determined using a commercially available ELISA kit.


RESULTS
A significant reduction in erythrocyte catalase activity in patients with isolated HCV infection, isolated SHF and those co-infected with SHF and HCV compared with the control group was found (P < 0.05). A similar pattern was found regarding erythrocyte glutathione content. Conversely TBARS level were significantly increased in patients with HCV, SHF and mixed groups compared with the control group (P < 0.05). Plasma IL-4-values were significantly increased in the three groups compared to the control subjects group. Furthermore, plasma IL-4 was significantly higher in patients with isolated SHF and those with SHF + HCV compared to the HCV alone patient group. Plasma IL-4 also correlated positively with portal vein diameter in SHF and SHF . HCV groups. (r = 0.54 and P < 0.05). Furthermore when all patients were analysed collectively, there was a positive correlation between plasma IL-4 and right lobe of the liver and plasma TBARS concentration.


CONCLUSIONS
Schistosomal infection triggers a Th2 type immune response as indicated by the high plasma IL-4. It also triggers an increase in reactive oxygen species levels. These effects especially IL-4 lead to more reduction in the level of antioxidants enzymes (that may be already compromised in malnourished schistosomal patients) with the resultant disease progression and development of complications.
Elsammak
M Y
MY
Departments of Chemical Pathology, Teaching Hospital, Alexandria University, Alexandria, Egypt. myelsammak@doctors.org.uk
Al-Sharkaweey
R M
RM
Ragab
M S
MS
Amin
G A
GA
Kandil
M H
MH
D000328:Adult; D002374:Catalase / Q000378:metabolism; D004534:Egypt; D004912:Erythrocytes / Q000737:chemistry / Q000201:enzymology; D005260:Female; D005978:Glutathione / Q000032:analysis; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D015847:Interleukin-4 / Q000097:blood*; D008099:Liver / Q000276:immunology / Q000469:parasitology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000473:pathology; D017382:Reactive Oxygen Species / Q000097:blood*; D012552:Schistosomiasis / Q000150:complications* / Q000276:immunology / Q000473:pathology*
D017382:Reactive Oxygen Species; D015847:Interleukin-4; D002374:Catalase; D005978:Glutathione