Nitric oxide downregulates lung macrophage inflammatory cytokine production.
BACKGROUND
Inflammatory cytokine production contributes to lung injury after lung ischemia reperfusion and during lung transplant rejection. Although nitric oxide has been demonstrated to reduce lung injury associated with the adult respiratory distress syndrome, it remains unknown whether the mechanism of nitric oxide's beneficial effects involves reducing lung macrophage inflammatory cytokine production. The purpose of this study was to determine whether nitric oxide downregulates lung macrophage inflammatory cytokine production.


METHODS
Lung macrophages were harvested by bronchoalveolar lavage (10(6) macrophage per milliliter from normal Sprague-Dawley rats, 6 animals per group) and treated under ex vivo tissue culture conditions with the nitric oxide releasing compound S-nitoso-N-acetyl-D, L-penicillamine (0, 10(-5) 10(-4), 10(-3), 10(-2) mol/L) before induction of inflammatory cytokines with endotoxin, (50 ng/mL for 24 hours). Supernatants were assayed for inflammatory cytokine production (tumor necrosis factor alpha, interleukin-1beta) by enzyme-linked immunosorbent assay.


RESULTS
Continuous nitric oxide release by S-nitoso-N-acetyl-D, L-penicillamine decreased lung macrophage tumor necrosis factor-alpha and interleukin-1beta production in a dose-dependent fashion (6 rats per group; data were analyzed for significance [p < 0.05] using two-way analysis of variance with Tukey's post-hoc correction).


CONCLUSIONS
Nitric oxide decreases inflammatory cytokine production by lung macrophage. The mechanism of nitric oxide's beneficial effects may be partially attributable to decreased production of inflammatory cytokines. Nitric oxide may serve an expanded role for reducing inflammatory cytokine production during acute lung injury, ischemia-reperfusion-induced inflammation, or lung transplant rejection.
Meldrum
D R
DR
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
Shames
B D
BD
Meng
X
X
Fullerton
D A
DA
McIntyre
R C
RC
Grover
F L
FL
Harken
A H
AH
D000818:Animals; D002478:Cells, Cultured; D004112:Dimercaprol; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D007375:Interleukin-1 / Q000096:biosynthesis*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; C110881:S-nitro-N-acetylpenicillamine; D014409:Tumor Necrosis Factor-alpha; D004112:Dimercaprol; D009569:Nitric Oxide; D010396:Penicillamine