Balance between alveolar macrophage IL-6 and TGF-beta in lung-transplant recipients. Marseille and Montréal Lung Transplantation Group.
Acute inflammation in the lung is characterized by a phase of tissue injury followed by a phase of tissue repair. When the latter is excessive, fibrosis occurs. Alveolar macrophages (AM) can produce cytokines involved in both phases of acute lung inflammation, notably interleukin-6 (IL-6), involved in injury and transforming growth factor-beta (TGF-beta), mediating repair. We hypothesized that AM were activated in both phases, and studied IL-6 and TGF-beta production by AM during complications of lung transplantation, acute rejection (AR), and cytomegalovirus pneumonitis (CMVP). In addition, we analyzed these cytokines in bronchiolitis obliterans (BO), a fibrotic complication of lung transplantation linked to previous AR and CMVP. At the onset of AR and CMVP, IL-6 secretion increased, whereas AM TGF-beta content was increased, but not its secretion. In contrast, with time, IL-6 reached control value whereas TGF-beta secretion rose significantly. In BO, IL-6 was not oversecreted, but TGF-beta increased, notably before functional abnormalities occurred. These results show that during acute complications of lung transplantation, AM display an early activation with oversecretion of IL-6, which is involved in tissue injury, counterbalanced by a late activation in which TGF-beta predominates, mediating tissue repair. The results provide new insights into the pathogenesis of BO, which is linked to acute complications of lung transplantation through this biphasic AM activation.
Magnan
A
A
Chest Medicine and Allergy Department, U INSERM 387, St.-Marguerite Hospital, Marseilles, France.
Mege
J L
JL
Escallier
J C
JC
Brisse
J
J
Capo
C
C
Reynaud
M
M
Thomas
P
P
Meric
B
B
Garbe
L
L
Badier
M
M
Viard
L
L
Bongrand
P
P
Giudicelli
R
R
Metras
D
D
Fuentes
P
P
Vervloet
D
D
Noirclerc
M
M
D000293:Adolescent; D000328:Adult; D001989:Bronchiolitis Obliterans / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002648:Child; D003586:Cytomegalovirus Infections / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation / Q000473:pathology / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011024:Pneumonia, Viral / Q000378:metabolism; D011183:Postoperative Complications; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D015850:Interleukin-6; D016212:Transforming Growth Factor beta