Interleukin-10 in human heart transplantation: an in situ hybridization study. The Manchester Transplant Cytokine Group.
BACKGROUND
The role of interleukin-10 in graft acceptance and rejection was investigated by analysis of its messenger RNA expression within endomyocardial biopsy material from heart transplant recipients.


METHODS
Forty-six biopsy specimens were analyzed from 19 patients (16 male, 3 female), with an age range of 15 to 62 years (mean = 47 years). Biopsy specimens were "snap" frozen in liquid nitrogen, and 10-microns thick sections were cut and postfixed in 4% paraformaldehyde. Messenger RNA for interleukin-10 was localized with nonradioactively (digoxigenin) labeled complementary DNA probes and detected immunoenzymatically with an antidigoxigenin polyclonal antibody. The histopathologic diagnosis of rejection was made according to the criteria of the Heart Rejection Study group.


RESULTS
Interleukin-10 transcripts were detected in 12 of 36 rejecting biopsy specimens. None of the ten nonrejecting biopsy specimens were positive. Expression within the rejection infiltrate was more prominent in biopsy specimens from milder rejection episodes. By contrast, in biopsy specimens from moderate rejection, expression was mainly within areas of fibrosis. The expression of interleukin-10 transcripts did not relate to the number of previous rejection episodes nor to the histologic grade of the subsequent biopsy specimens.


CONCLUSIONS
This study emphasizes the importance of in situ techniques in localizing cytokine expression in relation to tissue structure and suggests that interleukin-10 may serve a function in the immune regulation of the infiltrate at sites of inflammation, rather than in immune suppression of the rejection process. Further study is necessary to elucidate the precise role of interleukin-10 in transplantation in relation to the overall profile of cytokine expression within the rejection infiltrate.
Azzawi
M
M
Department of Biological Sciences, Manchester University, United Kingdom.
Hasleton
P S
PS
Grant
S C
SC
Stewart
J P
JP
Hutchinson
I V
IV
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D015342:DNA Probes; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D017403:In Situ Hybridization; D016753:Interleukin-10 / Q000032:analysis* / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis
D015342:DNA Probes; D012333:RNA, Messenger; D016753:Interleukin-10