title: Expression of cytokine messenger RNA after heart transplantation: relationship with rejection and serum cytokines.
abstract: Different groups of cytokines may initiate or inhibit the rejection process. We used the polymerase chain reaction to study the expression of cytokine mRNA for interleukin (IL)-2, -4, -6 and -10, tumor necrosis factor-alpha, and interferon-gamma in 187 biopsy specimens from 24 human cardiac transplant recipients 5-555 days after transplantation. Cytokine levels in the serum were also measured. Cytokine mRNA was detected in 38.5% of biopsy specimens. IL-10 mRNA was detected more frequently with mild or absent rejection (11.6% in grades 0 and 1 - vs. 1.4% in grades 2 and 3, P=0.01). Up to 90 days after transplantation, IL-2 mRNA was detected more frequently with moderate rejection (13% in grades 2 and 3 vs. 0% in grades 0 and 1, P=0.076), and IL-4 mRNA was detected more frequently with mild or absent rejection (16% in grades 0 and 1 - vs. 0% in grades 2 and 3, P=0.061). More than 90 days after transplantation, IL-2 mRNA was detected more frequently with mild or absent rejection (10% in grades 0 and 1 vs. 0% in grades 2 and 3, P=0.078). Serum IL-4 levels corresponding to biopsy specimens positive for IL-4 mRNA were higher than those corresponding to specimens negative for IL-4 mRNA (59 pg/ml vs. 32 pg/ml medians, P=0.028). Our results suggest that IL-10 and possibly IL-4 (T helper 2 cytokines) may suppress graft rejection, whereas IL-2 (T helper 1 cytokine) may promote cellular rejection. In addition, cytokine profiles may change with length of time after transplantation. The association of elevated serum levels of IL-4 with increased expression of intragraft IL-4 mRNA may suggest release of this cytokine from the graft into the circulation.
authors.affiliation: Department of Cardiology, Transplant Unit, Wythenshawe Hospital, Manchester, England.
authors.forename: S C
authors.initials: SC
authors.lastname: Grant
authors.forename: S P
authors.initials: SP
authors.lastname: Guy
authors.forename: W R
authors.initials: WR
authors.lastname: Lamb
authors.forename: N H
authors.initials: NH
authors.lastname: Brooks
authors.forename: P E
authors.initials: PE
authors.lastname: Brenchley
authors.forename: I V
authors.initials: IV
authors.lastname: Hutchinson
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood*; D005260:Female; D006084:Graft Rejection / Q000097:blood* / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis* / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger