Reviewer's report 
 Loss of interleukin-12 modifies the pro-inflammatory response but does not prevent duct Title: 
obstruction in experimental biliary atresia 
 1  21 February 2006 Version: Date: 
 Jiin-Haur Chuang Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
The authors describe in this article that loss of IL-12 does not prevent the development of 
experimental biliary atresia in newborn mice infected with rhesus rotavirus (RRV). They argue that the observed phenotype is caused by persistently high levels of neutrophil infiltration up to 2 weeks in the liver of IL-12-deficient mice and increased, though low, levels of IFN? mRNA. The article is 
organized in a very concise format. It is acceptable at its present form with high priority. Some minor 
comments may help to make the description clearer to the readers: 
1. In Figure 1 and 2, the number of mice in WT and IL-12KO group was N=15-21. However, from the 
Results section, we know that the survival of the animals is less than 10% beyond 3 weeks. We 
don’t know how many animals died in the disease process. Is N=15-21 equally present at each time 
point, or the number only represents the number of the animals enrolled in the study and the number 
varied at each time point. 
2. RRV infection in the IL-12KO group is associated with low levels of IFN? but high levels of IFNa. 
In a study by the authors’ group, it is interesting to note that the genetic knockout of interferon-? 
(IFN-?) in newborn Balb/c mice completely prevents the inflammatory and fibrotic obstruction of extrahepatic bile ducts after rotavirus infection. On the contrary, a single-dose therapy of IFN-a 
protects all rhesus rotavirus-infected pups from cholestatic diseases. In this study, a combined effect 
of lower IFN? and higher IFN-a in the IL-12KO group should theoretically protect the animal from 
RRV-induced biliary inflammation and obstruction. Is there presence of other mechanisms that 
counteract the effects of IFN-a or IFN?? What is the role of interferon regulatory factor (IRF) family in 
the disease process after RRV infection in the WT and IL-12KO groups? 
3. It is not clear what “amorphous tissue” means in the figure 4. 
In general, the materials contained in this article is appealing and interesting to the readers. I enjoy 
the privilege to review it. 
 Accept after discretionary revisions What next?: 
 An article of outstanding merit and interest in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Reviewer's report 
 Loss of interleukin-12 modifies the pro-inflammatory response but does not prevent duct Title: 
obstruction in experimental biliary atresia 
 1  21 February 2006 Version: Date: 
 Jiin-Haur Chuang Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
The authors describe in this article that loss of IL-12 does not prevent the development of 
experimental biliary atresia in newborn mice infected with rhesus rotavirus (RRV). They argue that the observed phenotype is caused by persistently high levels of neutrophil infiltration up to 2 weeks in the liver of IL-12-deficient mice and increased, though low, levels of IFN? mRNA. The article is 
organized in a very concise format. It is acceptable at its present form with high priority. Some minor 
comments may help to make the description clearer to the readers: 
1. In Figure 1 and 2, the number of mice in WT and IL-12KO group was N=15-21. However, from the 
Results section, we know that the survival of the animals is less than 10% beyond 3 weeks. We 
don’t know how many animals died in the disease process. Is N=15-21 equally present at each time 
point, or the number only represents the number of the animals enrolled in the study and the number 
varied at each time point. 
2. RRV infection in the IL-12KO group is associated with low levels of IFN? but high levels of IFNa. 
In a study by the authors’ group, it is interesting to note that the genetic knockout of interferon-? 
(IFN-?) in newborn Balb/c mice completely prevents the inflammatory and fibrotic obstruction of extrahepatic bile ducts after rotavirus infection. On the contrary, a single-dose therapy of IFN-a 
protects all rhesus rotavirus-infected pups from cholestatic diseases. In this study, a combined effect 
of lower IFN? and higher IFN-a in the IL-12KO group should theoretically protect the animal from 
RRV-induced biliary inflammation and obstruction. Is there presence of other mechanisms that 
counteract the effects of IFN-a or IFN?? What is the role of interferon regulatory factor (IRF) family in 
the disease process after RRV infection in the WT and IL-12KO groups? 
3. It is not clear what “amorphous tissue” means in the figure 4. 
In general, the materials contained in this article is appealing and interesting to the readers. I enjoy 
the privilege to review it. 
 Accept after discretionary revisions What next?: 
 An article of outstanding merit and interest in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Please review this paper.
user
Reviewer's report 
 Loss of interleukin-12 modifies the pro-inflammatory response but does not prevent duct Title: 
obstruction in experimental biliary atresia 
 1  21 February 2006 Version: Date: 
 Jiin-Haur Chuang Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
The authors describe in this article that loss of IL-12 does not prevent the development of 
experimental biliary atresia in newborn mice infected with rhesus rotavirus (RRV). They argue that the observed phenotype is caused by persistently high levels of neutrophil infiltration up to 2 weeks in the liver of IL-12-deficient mice and increased, though low, levels of IFN? mRNA. The article is 
organized in a very concise format. It is acceptable at its present form with high priority. Some minor 
comments may help to make the description clearer to the readers: 
1. In Figure 1 and 2, the number of mice in WT and IL-12KO group was N=15-21. However, from the 
Results section, we know that the survival of the animals is less than 10% beyond 3 weeks. We 
don’t know how many animals died in the disease process. Is N=15-21 equally present at each time 
point, or the number only represents the number of the animals enrolled in the study and the number 
varied at each time point. 
2. RRV infection in the IL-12KO group is associated with low levels of IFN? but high levels of IFNa. 
In a study by the authors’ group, it is interesting to note that the genetic knockout of interferon-? 
(IFN-?) in newborn Balb/c mice completely prevents the inflammatory and fibrotic obstruction of extrahepatic bile ducts after rotavirus infection. On the contrary, a single-dose therapy of IFN-a 
protects all rhesus rotavirus-infected pups from cholestatic diseases. In this study, a combined effect 
of lower IFN? and higher IFN-a in the IL-12KO group should theoretically protect the animal from 
RRV-induced biliary inflammation and obstruction. Is there presence of other mechanisms that 
counteract the effects of IFN-a or IFN?? What is the role of interferon regulatory factor (IRF) family in 
the disease process after RRV infection in the WT and IL-12KO groups? 
3. It is not clear what “amorphous tissue” means in the figure 4. 
In general, the materials contained in this article is appealing and interesting to the readers. I enjoy 
the privilege to review it. 
 Accept after discretionary revisions What next?: 
 An article of outstanding merit and interest in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
assistant