Airway hyperresponsiveness induced by repetitive intraperitoneal injection of lipopolysacharide and the involvement of inflammation and nitric oxide in guinea pigs.
OBJECTIVE
Airway hyperresponsiveness (AHR) is involved in bronchial asthma and chronic obstructive pulmonary disease (COPD) and produces respiratory symptoms. Lipopolysaccharide (LPS) has been found to be significantly related to the severity of asthma. However, its clinical mechanism still remains controversial. This study investigated the in vivo effect of repetitive intraperitoneal administration of lipopolysaccharide (LPS) on airway hyperresponsiveness (AHR) in guinea pigs and the possible involvement of inflammation, nitric oxide (NO) and nitric oxide synthase (NOS).


METHODS
There were two exposure groups for intraperitoneal LPS injection: (1) LPS was given at a dose of 1 mg x kg(-1), followed by sterile saline (NS) 1 ml x kg(-1) 8 h later every 24 h; (2) LPS was given at a dose of 0.5 mg x kg(-1) two times with an interval of 8 h every 24 h. Each exposure regime was repeated 4 times. Control animals were given NS and 6 naive guinea pigs were used as baseline control. Determinations were made 24 h after each exposure.


RESULTS
Persistent AHR occurred 24 h after the third and fourth exposures to LPS in the first exposure group (at one dose), but occurred earlier after the exposures to LPS in the second exposure group (at divided doses). The numbers of total cells and neutrophils were elevated initially but subsided subsequently in LPS-treated groups. No evidence of morphological changes in the small airways was found 24 h after any of the exposures. The Ca(2+)-dependent and Ca(2+)-independent NOS activities (mainly produced by iNOS) in the BALF, as well as the production of NO, were significantly elevated 24 h after any of third and fourth exposures in LPS-treated groups.


CONCLUSIONS
Our results demonstrate that repetitive intraperitoneal LPS can induce persistent AHR which occurs earlier when the frequency of injection increase, and an elevation of NO production and iNOS activity may be involved in is systemic-LPS-induced AHR.
Jiang
H
H
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, China.
Qu
J
J
He
L
L
Pan
J
J
Chen
X
X
Li
L
L
Zhu
D
D
Cao
Y
Y
D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D013997:Time Factors
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D006632:Histamine; D019001:Nitric Oxide Synthase; D002118:Calcium