Macrophage endotoxin tolerance. Tumor necrosis factor and interleukin-1 regulation by lipopolysaccharide pretreatment
S. C. Seatter, T. Bennet, M. H. Li, M. P. Bubrick and M. A. West
Department of Surgery, Hennepin County Medical Center, University of Minnesota, Minneapolis.
OBJECTIVE: To correlate cytokine gene expression with the release of
protein product by murine peritoneal macrophages rendered tolerant by
sequential endotoxin stimulation in vitro. DESIGN: In vitro investigation
of the regulation of endotoxin-stimulated cytokine production following
endotoxin pretreatment using cytokine bioassays, polymerase chain reaction,
and Northern blot analyses. SETTING: In vitro cell culture model of
sequential endotoxin stimulation of murine macrophages. INTERVENTIONS:
Macrophages were pretreated with 0 or 100 ng/mL of lipopolysaccharide
(LPS1) for 24 hours and then stimulated with 0 or 100 ng/mL of LPS (LPS2)
for 4 or 24 hours. After stimulation, supernatant tumor necrosis factor
(TNF) and interleukin-1 (IL-1) levels were measured by bioassay. Total RNA
was extracted and messenger RNA (mRNA) corresponding to TNF and IL-1 was
amplified by reverse transcription-polymerase chain reaction or analyzed by
Northern blot. RESULTS: Endotoxin pretreatment resulted in the augmentation
of IL-1 (mean +/- SD, 78 +/- 9 vs 596 +/- 42 pg/mL, P < .01) and the
inhibition of TNF (274 +/- 63 vs 61 +/- 3 pg/mL, P < .01) release 4
hours after stimulation with 100 ng/mL of LPS2. A similar pattern of
cytokine release was observed 24 hours after LPS2 stimulation. Pretreatment
produced an increased IL-1 message in response to 100 ng/mL of LPS2. The
TNF message was detectable in all groups receiving LPS2 alone, but the
highest levels of TNF mRNA were seen in LPS1-pretreated cells stimulated
with LPS2. CONCLUSIONS: Endotoxin pretreatment produced increased IL-1
message that paralleled the augmentation of IL-1 protein, whereas abundant
TNF message was present even though TNF protein release was significantly
inhibited. In this model of in vitro endotoxin tolerance, pretreatment
initiates divergent pathways of cytokine regulation.
Inhibition of a p38/Stress-Activated Protein Kinase-2-Dependent Phosphatase Restores Function of IL-1 Receptor-Associated Kinase-1 and Reverses Toll-Like Receptor 2- and 4-Dependent Tolerance of Macrophages
Ropert et al.
J. Immunol. 2003;171:1456-1465.
ABSTRACT
| FULL TEXT
Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline
Porter et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000;279:R2113-R2120.
ABSTRACT
| FULL TEXT
A Limulus Antilipopolysaccharide Factor-Derived Peptide Exhibits a New Immunological Activity with Potential Applicability in Infectious Diseases
Vallespi et al.
CVI 2000;7:669-675.
ABSTRACT
| FULL TEXT
Dissociation of IFN-{gamma} from IL-12 and IL-18 production during endotoxin tolerance
Rayhane et al.
Innate Immunity 1999;5:319-324.
ABSTRACT
Bacterial Priming Increases Lung Injury in Gram-negative Sepsis
WELTY-WOLF et al.
Am. J. Respir. Crit. Care Med. 1998;158:610-619.
ABSTRACT
| FULL TEXT
TNF-alpha tolerance blocks LPS-induced hypophagia but LPS tolerance fails to prevent TNF-alpha -induced hypophagia
Porter et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 1998;274:R741-R745.
ABSTRACT
| FULL TEXT
Endotoxin-induced cytokine release from whole blood - similarities between monocyte dysfunction in septic disease and during postoperative acute phase response
Berger et al.
Innate Immunity 1997;4:17-24.
ABSTRACT
The protein kinase C activator PMA modulates LPS lethality in normal mice and protects against LPS lethality in D-galactosamine-sensitized mice
Silverstein et al.
Innate Immunity 1996;3:29-37.
ABSTRACT
Preclinical and clinical evaluation of carbohydrate immunopharmaceuticals in the prevention of sepsis and septic sequelae
Williams et al.
Innate Immunity 1995;2:203-208.
ABSTRACT
