Reviewer's report
 Melatonin reduces cytokine induced expression of MAdCAM-1: Implications for IBD therapy. Title:
Authors:
Makotoh Sasaki MD (msasak@lsuhsc.edu )
Paul Jordan MD (pjorda1@lsuhsc.edu )
Takashi Joh MD (jalexa@lsuhsc.edu )
Makotoh Itoh MD (jalexa@lsuhsc.edu )
Michael Jenkins (michael.jenkins@virgin.net )
J. Steven Alexander PhD (jalexa@lsuhsc.edu )
 1  3 Mar 2002 Version: Date:
 Dr Soichiro Miura Reviewer:
 A paper whose findings are important to those with closely related research interests Level of interest:
 Unable to decide on acceptance or rejection until the authors have responded Advice on publication:
to the compulsory revisions
In this manuscript authors found that melatonin significantly attenuated endothelial MAdCAM-1 
expression induced by TNF-a in vitro. 
This is a concise paper that includes an interesting effect of melatonin, but it does not directly indicate that melatonin may exert therapeutic activity in IBD. Moreover the attenuating mechanism of melatonin on MAdCAM-1 upregulation is only speculative. I have several concerns as follows: 
1) This study does not show a direct evidence that melatonin exert therapeutic activity in IBD. Recently 
Cuzzocrea S. et al. reported that melatonin reduces dinitrobenzene sulfonic acid-induced colitis (J. Pineal Res 30: 1-12, 2001). Therefore, implication of melatonin for IBD therapy itself should not be 
stressed throughout this paper, especially must not be appeared in the title. 
2) Instead, the concentrations of melatonin by which MAdCAM-1 was inhibited must be discussed more 
in detail comparing the previous reports of in vivo effect of melatonin on intestinal injury. In addition is 
this concentration more than 100 uM safe and well-tolerated dose in in vivo situation? 
3) Because the inhibitory effect of melatonin on MAdCAM-1 is the main finding of this paper, its 
mechanism of action is only speculative. Authors should show whether MAdCAM-1 expression is mediated through the NF-kB system as they did in the paper by Oshima et al. 
Minor point: 
1) Method-Western analysis. Rat anti MAdCAM-1 mAb should be Rat anti- mouse MAdCAM-1 mAb. 
Competing interests:
None declared.
Reviewer's report
 Melatonin reduces cytokine induced expression of MAdCAM-1: Implications for IBD therapy. Title:
Authors:
Makotoh Sasaki MD (msasak@lsuhsc.edu )
Paul Jordan MD (pjorda1@lsuhsc.edu )
Takashi Joh MD (jalexa@lsuhsc.edu )
Makotoh Itoh MD (jalexa@lsuhsc.edu )
Michael Jenkins (michael.jenkins@virgin.net )
J. Steven Alexander PhD (jalexa@lsuhsc.edu )
 1  3 Mar 2002 Version: Date:
 Dr Soichiro Miura Reviewer:
 A paper whose findings are important to those with closely related research interests Level of interest:
 Unable to decide on acceptance or rejection until the authors have responded Advice on publication:
to the compulsory revisions
In this manuscript authors found that melatonin significantly attenuated endothelial MAdCAM-1 
expression induced by TNF-a in vitro. 
This is a concise paper that includes an interesting effect of melatonin, but it does not directly indicate that melatonin may exert therapeutic activity in IBD. Moreover the attenuating mechanism of melatonin on MAdCAM-1 upregulation is only speculative. I have several concerns as follows: 
1) This study does not show a direct evidence that melatonin exert therapeutic activity in IBD. Recently 
Cuzzocrea S. et al. reported that melatonin reduces dinitrobenzene sulfonic acid-induced colitis (J. Pineal Res 30: 1-12, 2001). Therefore, implication of melatonin for IBD therapy itself should not be 
stressed throughout this paper, especially must not be appeared in the title. 
2) Instead, the concentrations of melatonin by which MAdCAM-1 was inhibited must be discussed more 
in detail comparing the previous reports of in vivo effect of melatonin on intestinal injury. In addition is 
this concentration more than 100 uM safe and well-tolerated dose in in vivo situation? 
3) Because the inhibitory effect of melatonin on MAdCAM-1 is the main finding of this paper, its 
mechanism of action is only speculative. Authors should show whether MAdCAM-1 expression is mediated through the NF-kB system as they did in the paper by Oshima et al. 
Minor point: 
1) Method-Western analysis. Rat anti MAdCAM-1 mAb should be Rat anti- mouse MAdCAM-1 mAb. 
Competing interests:
None declared.
Please review this paper.
user
Reviewer's report
 Melatonin reduces cytokine induced expression of MAdCAM-1: Implications for IBD therapy. Title:
Authors:
Makotoh Sasaki MD (msasak@lsuhsc.edu )
Paul Jordan MD (pjorda1@lsuhsc.edu )
Takashi Joh MD (jalexa@lsuhsc.edu )
Makotoh Itoh MD (jalexa@lsuhsc.edu )
Michael Jenkins (michael.jenkins@virgin.net )
J. Steven Alexander PhD (jalexa@lsuhsc.edu )
 1  3 Mar 2002 Version: Date:
 Dr Soichiro Miura Reviewer:
 A paper whose findings are important to those with closely related research interests Level of interest:
 Unable to decide on acceptance or rejection until the authors have responded Advice on publication:
to the compulsory revisions
In this manuscript authors found that melatonin significantly attenuated endothelial MAdCAM-1 
expression induced by TNF-a in vitro. 
This is a concise paper that includes an interesting effect of melatonin, but it does not directly indicate that melatonin may exert therapeutic activity in IBD. Moreover the attenuating mechanism of melatonin on MAdCAM-1 upregulation is only speculative. I have several concerns as follows: 
1) This study does not show a direct evidence that melatonin exert therapeutic activity in IBD. Recently 
Cuzzocrea S. et al. reported that melatonin reduces dinitrobenzene sulfonic acid-induced colitis (J. Pineal Res 30: 1-12, 2001). Therefore, implication of melatonin for IBD therapy itself should not be 
stressed throughout this paper, especially must not be appeared in the title. 
2) Instead, the concentrations of melatonin by which MAdCAM-1 was inhibited must be discussed more 
in detail comparing the previous reports of in vivo effect of melatonin on intestinal injury. In addition is 
this concentration more than 100 uM safe and well-tolerated dose in in vivo situation? 
3) Because the inhibitory effect of melatonin on MAdCAM-1 is the main finding of this paper, its 
mechanism of action is only speculative. Authors should show whether MAdCAM-1 expression is mediated through the NF-kB system as they did in the paper by Oshima et al. 
Minor point: 
1) Method-Western analysis. Rat anti MAdCAM-1 mAb should be Rat anti- mouse MAdCAM-1 mAb. 
Competing interests:
None declared.
assistant