Expression of interleukin-6 in association with rat lung reimplantation and allograft rejection.
Organ transplantation has become a therapeutic option for the replacement of malfunctioning tissues and organs. Since the advent of the first combined heart-lung transplant in 1981, there has been a rapid growth in the popularity of lung transplantation for a number of end-stage pulmonary disorders. Interestingly, these lung transplant patients experience more complications of acute and chronic allograft rejection compared with recipients of other solid organs. These episodes of rejection are related to a complex series of events that depend on the interaction of many cells and soluble mediators leading to cellular and tissue injury. The histopathology of lung allograft rejection has been actively studied and is associated with the sequestration of activated mononuclear phagocytes, T and B lymphocytes. These cells secrete a number of soluble mediators, that is, cytokines, that participate in the evolution of the immune response via autocrine, paracrine, or endocrine mechanisms. The interaction of cytokines with their targets leads to cellular activation, proliferation, and differentiation. In this study, we postulated that interleukin-6 (IL-6) may have a central role in the pathogenesis of acute lung allograft rejection. To test this hypothesis, we employed an unmodified RT1-incompatible rat lung allograft model and assessed the time course and major tissue compartment(s) of IL-6 production during the evolution of lung allograft rejection. The expression and production of IL-6 during the pathogenesis of lung allograft rejection was measured at the whole-animal, organ, cellular, and molecular levels. The expression of IL-6 was found to be bimodal in character, initially related to the reimplantation response and finally to the maximal allograft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
Rolfe
M W
MW
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
Kunkel
S L
SL
Demeester
S R
SR
Swiderski
D L
DL
Lincoln
P M
PM
Deeb
G M
GM
Strieter
R M
RM
D000818:Animals; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D015850:Interleukin-6 / Q000032:analysis* / Q000235:genetics; D008168:Lung / Q000737:chemistry* / Q000473:pathology; D016040:Lung Transplantation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014185:Transplantation, Isogeneic
D015850:Interleukin-6; D012333:RNA, Messenger