PMID- 9673235
OWN - NLM
STAT- MEDLINE
DCOM- 19980820
LR  - 20240409
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 66
IP  - 8
DP  - 1998 Aug
TI  - Pulmonary and hepatic gene expression following cecal ligation and puncture: 
      monophosphoryl lipid A prophylaxis attenuates sepsis-induced cytokine and 
      chemokine expression and neutrophil infiltration.
PG  - 3569-78
AB  - Polymicrobial sepsis induced by cecal ligation and puncture (CLP) reproduces many 
      of the pathophysiologic features of septic shock. In this study, we demonstrate 
      that mRNA for a broad range of pro- and anti-inflammatory cytokine and chemokine 
      genes are temporally regulated after CLP in the lung and liver. We also assessed 
      whether prophylactic administration of monophosphoryl lipid A (MPL), a nontoxic 
      derivative of lipopolysaccharide (LPS) that induces endotoxin tolerance and 
      attenuates the sepsis syndrome in mice after CLP, would alter tissue-specific 
      gene expression post-CLP. Levels of pulmonary interleukin-6 (IL-6), tumor 
      necrosis factor alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), 
      IL-1 receptor antagonist (IL-1ra), and IL-10 mRNA, as well as hepatic IL-1beta, 
      IL-6, gamma interferon (IFN-gamma), G-CSF, inducible nitric oxide synthase, and 
      IL-10 mRNA, were reduced in MPL-pretreated mice after CLP compared to control 
      mice. Chemokine mRNA expression was also profoundly mitigated in MPL-pretreated 
      mice after CLP. Specifically, levels of pulmonary and hepatic macrophage 
      inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, MIP-2, and monocyte 
      chemoattractant protein-1 (MCP-1) mRNA, as well as hepatic IFN-gamma-inducible 
      protein 10 and KC mRNA, were attenuated in MPL-pretreated mice after CLP. 
      Attenuated levels of IL-6, TNF-alpha, MCP-1, MIP-1alpha, and MIP-2 in serum also 
      were observed in MPL-pretreated mice after CLP. Diminished pulmonary chemokine 
      mRNA production was associated with reduced neutrophil margination and pulmonary 
      myeloperoxidase activity. These data suggest that prophylactic administration of 
      MPL mitigates the sepsis syndrome by reducing chemokine production and the 
      recruitment of inflammatory cells into tissues, thereby attenuating the 
      production of proinflammatory cytokines.
FAU - Salkowski, C A
AU  - Salkowski CA
AD  - Department of Microbiology and Immunology, Uniformed Services University of the 
      Health Sciences, Bethesda, Maryland 20814, USA.
FAU - Detore, G
AU  - Detore G
FAU - Franks, A
AU  - Franks A
FAU - Falk, M C
AU  - Falk MC
FAU - Vogel, S N
AU  - Vogel SN
LA  - eng
GR  - R01 AI018797/AI/NIAID NIH HHS/United States
GR  - R37 AI018797/AI/NIAID NIH HHS/United States
GR  - R56 AI018797/AI/NIAID NIH HHS/United States
GR  - AI-18797/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Lipid A)
RN  - 0 (RNA, Messenger)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - MWC0ET1L2P (monophosphoryl lipid A)
SB  - IM
MH  - Adjuvants, Immunologic/*pharmacology
MH  - Animals
MH  - Cecum/injuries
MH  - Chemokines/*biosynthesis/genetics
MH  - Cytokines/*biosynthesis/genetics
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/drug effects
MH  - Immune Tolerance
MH  - Kinetics
MH  - Lipid A/*analogs & derivatives/pharmacology
MH  - Liver/*immunology
MH  - Lung/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neutrophils/*immunology
MH  - Nitric Oxide Synthase/biosynthesis/genetics
MH  - Nitric Oxide Synthase Type II
MH  - RNA, Messenger
MH  - Sepsis/genetics/*immunology
PMC - PMC108388
EDAT- 1998/07/23 00:00
MHDA- 1998/07/23 00:01
PMCR- 1998/08/01
CRDT- 1998/07/23 00:00
PHST- 1998/07/23 00:00 [pubmed]
PHST- 1998/07/23 00:01 [medline]
PHST- 1998/07/23 00:00 [entrez]
PHST- 1998/08/01 00:00 [pmc-release]
AID - 1499 [pii]
AID - 10.1128/IAI.66.8.3569-3578.1998 [doi]
PST - ppublish
SO  - Infect Immun. 1998 Aug;66(8):3569-78. doi: 10.1128/IAI.66.8.3569-3578.1998.