Interleukin 6 and interferon-gamma gene expression in lung transplant recipients with refractory acute cellular rejection: implications for monitoring and inhibition by treatment with aerosolized cyclosporine.
BACKGROUND
The purpose of this study was to correlate cytokine gene expression from bronchoalveolar lavage (BAL) cells and peripheral blood lymphocytes (PBL) with graft histology in recipients with persistent acute rejection treated with aerosolized cyclosporine (ACsA).


METHODS
We measured mRNA for interleukin (IL) 6, interferon (IFN)-gamma, and IL-10 in recipients (1) without rejection (n=13), (2) with acute rejection that responded to pulsed methylprednisolone (n=7), and (3) with "refractory" acute rejection that failed to respond to conventional immunosuppression (n=17). In the latter group, ACsA was initiated.


RESULTS
BAL cell IL-6 and IFN-gamma were highest in recipients with refractory rejection compared with recipients with steroid-responsive rejection and recipients with no rejection. Improvement in rejection histology occurred in 15 of 17 recipients who were treated with ACsA. IL-6 and IFN-gamma mRNA levels from BAL cells decreased during treatment with ACsA (median IL-6:actin ratio: before treatment, 0.40 vs. after treatment, 0.003, P=0.001; IFN-gamma:actin ratio: before treatment, 0.32 vs. after treatment, 0.04, P=0.001). PBL IL-6 and IFN-gamma mRNA expression also decreased during ACsA treatment after 180 days. Expression of IL-10 mRNA from BAL and PBL did not change during ACsA treatment (0.0 vs. 0.03 and 0.0 vs. 0.02, respectively).


CONCLUSIONS
IL-6 and IFN-gamma mRNA expression from BAL cells was highest in those recipients with refractory histologic acute rejection. ACsA was associated with decreased IFN-gamma and IL-6 gene expression in BAL cells and PBL.
Iacono
A
A
Department of Medicine, University of Pittsburgh, Pennsylvania, USA. aldo-iacono@paccm.pitt.edu
Dauber
J
J
Keenan
R
R
Spichty
K
K
Cai
J
J
Grgurich
W
W
Burckart
G
G
Smaldone
G
G
Pham
S
S
Ohori
N P
NP
Yousem
S
S
Williams
P
P
Griffith
B
B
Zeevi
A
A
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics / Q000517:prevention & control; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D012333:RNA, Messenger / Q000378:metabolism; D014184:Transplantation, Homologous / Q000473:pathology
D000336:Aerosols; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D012333:RNA, Messenger; D007371:Interferon-gamma; D016572:Cyclosporine