Exogenous nitric oxide can control SIRS and downregulate NFkappaB.
BACKGROUND
Nitric oxide (NO) participates in inflammation and affects almost all steps of its development. Several experimental studies have unveiled the beneficial effects of NO through modulation of the Systemic Inflammatory Response Syndrome (SIRS). In this sense, in the present work we attempted to evaluate the beneficial effects of exogenous NO and its levels of action (biochemical and cellular) in a model of SIRS induced by two sequential insults.


METHODS
Dacron graft implantation (first insult) and subsequent administration of Zymosan A (second insult) in Wistar rats. The animals were divided into four groups: 1) No manipulation (Basal); 2) Laparotomy (L) + mineral oil (Sham); 3) L + Graft-Zymosan (GZ) (Control); and 4) L + GZ + NO (Assay). Determinations: Survival, TNF-alpha, SOA, ICAM-1, and NFkappaB.


RESULTS
The model established (Control) induced a mortality rate of 20%. Also, it significantly increased the levels of TNF-alpha (P <0.001) and SOA (P <0.01), ICAM-1 expression, and NFkappaB levels (P <0.05). Treatment with NO reduced mortality to 0%, significantly decreasing TNF-alpha (P <0.001) and SOA (P <0.01) levels, ICAM-1 expression, and NFkappaB levels (P <0.05).


CONCLUSIONS
The exogenous administration of NO before the two sequential insults controlled SIRS at biochemical level (TNF-alpha, SOA) and at cellular level (transcription) in a lasting manner. The cascade-like interrelationship of both levels and the study design do not allow us the pinpoint the key to its modulation.
Lozano
Francisco S
FS
Department of Vascular Surgery, University Hospital, University of Salamanca, Salamanca, Spain.
Barros
Marcello B
MB
García-Criado
Francisco J
FJ
Gomez-Alonso
Alberto
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000276:immunology / Q000627:therapeutic use*; D001672:Biocompatible Materials / Q000009:adverse effects; D015415:Biomarkers; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects; D015536:Down-Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008297:Male; D023421:Models, Animal; D016328:NF-kappa B / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology / Q000627:therapeutic use*; D011093:Polyethylene Terephthalates / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D016037:Single-Blind Method; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D015054:Zymosan / Q000009:adverse effects / Q000276:immunology; D047071:beta-Glucans / Q000009:adverse effects / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D015415:Biomarkers; D016328:NF-kappa B; D011093:Polyethylene Terephthalates; D047071:beta-Glucans; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D015054:Zymosan