Lung inflammation is induced by renal ischemia and reperfusion injury as part of the systemic inflammatory syndrome.
BACKGROUND
Ischemia and reperfusion injury (IRI) are mainly caused by leukocyte activation, endothelial dysfunction and production of reactive oxygen species. Moreover, IRI can lead to a systemic response affecting distant organs, such as the lungs.


OBJECTIVE
The objective was to study the pulmonary inflammatory systemic response after renal IRI.


METHODS
Male C57Bl/6 mice were subjected to 45 min of bilateral renal ischemia, followed by 4, 6, 12, 24 and 48 h of reperfusion. Blood was collected to measure serum creatinine and cytokine concentrations. Bronchoalveolar lavage fluid (BALF) was collected to determine the number of cells and PGE(2) concentration. Expressions of iNOS and COX-2 in lung were determined by Western blot. Gene analyses were quantified by real time PCR.


RESULTS
Serum creatinine increased in the IRI group compared to sham mainly at 24 h after IRI (2.57 +/- 0.16 vs. 0.43 +/- 0.07, p < 0.01). The total number of cells in BAL fluid was higher in the IRI group in comparison with sham, 12 h (100 x 10(4) +/- 15.63 vs. 18.1 x 10(4) +/- 10.5, p < 0.05) 24 h (124 x 10(4) +/- 8.94 vs. 23.2 x 10(4) +/- 3.5, p < 0.05) and 48 h (79 x 10(4) +/- 15.72 vs. 22.2 x 10(4) +/- 4.2, p < 0.05), mainly by mononuclear cells and neutrophils. Pulmonary COX-2 and iNOS were up-regulated in the IRI group. TNF-alpha, IL-1beta, MCP-1, KC and IL-6 mRNA expression were up-regulated in kidney and lungs 24 h after renal IRI. ICAM-1 mRNA was up-regulated in lungs 24 h after renal IRI. Serum TNF-alpha, IL-1beta and MCP-1 and BALF PGE(2) concentrations were increased 24 h after renal IRI.


CONCLUSIONS
Renal IRI induces an increase of cellular infiltration, up-regulation of COX-2, iNOS and ICAM-1, enhanced chemokine expression and a Th1 cytokine profile in lung demonstrating that the inflammatory response is indeed systemic, possibly leading to an amplification of renal injury.
Campanholle
G
G
Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, Av. Prof. Lineu Prestes, 1730, São Paulo, SP 05508-900, Brazil.
Landgraf
R G
RG
Gonçalves
G M
GM
Paiva
V N
VN
Martins
J O
JO
Wang
P H M
PH
Monteiro
R M M
RM
Silva
R C
RC
Cenedeze
M A
MA
Teixeira
V P A
VP
Reis
M A
MA
Pacheco-Silva
A
A
Jancar
S
S
Camara
Niels Olsen Saraiva
NO
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018925:Chemokines / Q000097:blood / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007668:Kidney / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D011014:Pneumonia / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D015427:Reperfusion Injury / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology / Q000503:physiopathology
D018925:Chemokines; D016207:Cytokines; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
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