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M A West

Publications and source records attributed to M A West.

At least 55 records · Page 3Linked to original sources
PubMed1996

Kinetics of decreased LPS-stimulated cytokine release by macrophages exposed to CO2.

The mechanisms responsible for the lack of inflammation after laparoscopic surgery remain unknown. Peritoneal macrophages (M phi) incubated in carbon dioxide (CO2) but not air or helium (He), had significant, reversible inhibition of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) and interleukin-1 (IL-1) release. In these experiments the kinetics of these C02-induced alterations in cytokine secretion were examined. Murine peritoneal Mphi were stimulated with LPS for 4 hr and incubated in different test gases (95% air/5% CO2,80%CO2/20%O2,80% He/20% O2) for intervals between 0.25 and 4 hr. Time between gas incubation and LPS stimulation was varied to determine the persistence of CO2 inhibition. Parallel M phi groups received LPS stimulation 24 hr later. Supernatant TNF and IL-1 were measured by bioassay and polymerase chain reaction was used to examine cytokine mRNA. Significant reversible inhibition of TNF and IL-1 was seen with CO2, but not He or air. Inhibition of IL-1 occurred 15 min after CO2 exposure, was associated with decreased IL-1 mRNA, and was rapidly lost following incubation in the control atmosphere. TNF inhibition was seen despite normal levels of TNF message, required more than 30 min of CO2 exposure, and persisted after CO2 removal. CO2 produced profound, reversible, inhibition of LPS-stimulated cytokine release by peritoneal Mphi. The transient inability to secrete inflammatory cytokines after CO2 exposure may explain the lack of systemic inflammation after laparoscopic surgery with CO2.

Animals↗
PubMed1996

A novel adaptor-related protein complex.

Coat proteins are required for the budding of the transport vesicles that mediate membrane traffic pathways, but for many pathways such proteins pathways, but for many pathways such proteins have not yet been identified. We have raised antibodies against p47, a homologue of the medium chains of the adaptor complexes of clathrin-coated vesicles (Pevsner, J., W. Volknandt, B.R. Wong, and R.H. Scheller. 1994. Gene (Amst.). 146:279-283), to determine whether this protein might be a component of a new type of coat. p47 coimmunoprecipitates with three other proteins: two unknown proteins of 160 and 25 kD, and beta-NAP, a homologue of the beta/beta'-adaptins, indicating that it is a subunit of an adaptor-like heterotetrameric complex. However, p47 is not enriched in preparations of clathrin-coated vesicles. Recruitment of the p47-containing complex onto cell membranes is stimulated by GTP gamma S and blocked by brefeldin A, indicating that, like other coat proteins, its membrane association is regulated by an ARF. The newly recruited complex is localized to non-clathrin-coated buds and vesicles associated with the TGN. Endogenous complex in primary cultures of neuronal cells is also localized to the TGN, and in addition, some complex is associated with the plasma membrane. These results indicate that the complex is a component of a novel type of coat that facilitates the budding of vesicles from the TGN, possibly for transporting newly synthesized proteins to the plasma membrane.

Adaptor Protein Complex 3↗
PubMed1996

Role of calcium in lipopolysaccharide-stimulated tumor necrosis factor and interleukin-1 signal transduction in naive and endotoxin-tolerant murine macrophages.

OBJECTIVE: Dysregulated macrophage cytokine production may predispose to organ failure during sepsis. Macrophages pretreated in vitro with low-dose endotoxin (LPSp) become "tolerant" to subsequent lipopolysaccharide (LPS) activation (LPSa), characterized by inhibition of tumor necrosis factor (TNF) and augmentation of interleukin-1 (IL-1). To understand cytokine dysregulation we examined the Ca2+ dependence of TNF and IL-1 signal transduction to LPSa and whether it was altered by LPSp. METHODS: Murine peritoneal exudate macrophages received +/- 100 ng/mL of LPSp for 24 hours. Cultures were pretreated for 2 hours with specific signal transduction inhibitors (verapamil, a Ca2+ channel inhibitor; TMB-8, an inhibitor of intracellular Ca2+ release; U73122, an inhibitor of phospholipase C; or W7, a calmodulin inhibitor) before 24 hours LPSa-stimulation. TNF and IL-1 mRNA were estimated 6 hours after LPSa by using reverse transcriptase polymerase chain reaction. Supernatant TNF and IL-1 were measured by bioassay. RESULTS: Treatment with verapamil, TMB-8, U73122, or W7 markedly inhibited TNF release by LPSa, but had little effect on IL-1 release. Reprogramming by LPSp did not alter the Ca2+ signal transduction pathways for either cytokine. U73122 and verapamil did prevent the augmentation of IL-1 release seen after LPSp. TNF message was present after LPSa despite reprogrammed inhibition of TNF protein by LPSp. Signal transduction inhibitors that blocked Ca2+ altered TNF and IL-1 message in reprogrammed macrophages in a pattern similar to their effects on naive cells. CONCLUSIONS: Intracellular Ca2+ is required for TNF protein release by naive macrophages and TNF mRNA transcription of both naive and LPSp reprogrammed cells, however LPSa-stimulated IL-1 release in peritoneal macrophages does not require Ca2+ dependent signaling pathways.

Animals↗
PubMed1996

Hypoxic alterations in cellular signal transduction in shock and sepsis.

Many different cellular processes are altered by microenvironmental changes in the oxygen level, particularly hypoxia. In most cases, these hypoxic effects are mediated via alterations in cellular signal transduction pathways. Low oxygen states are generally viewed as deleterious; however, recent studies show that alterations in oxygen levels are physiologically important, influencing cells in a variety of ways. Low oxygen levels can stimulate cellular processes, such as the production of tumor necrosis factor, interleukin (IL)-1, IL-8, and nuclear factor kappa B. Kupffer cell-mediated alterations in cocultured hepatocyte function are altered by pre-exposure to hypoxic culture conditions, whereas superoxide production, intracellular pH, and adenosine triphosphate levels are decreased by hypoxia. Hypoxia followed by reoxygenation stimulates tyrosine kinase enzymes and increases intracellular calcium in a variety of cells. This review highlights recent findings concerning the manner and mechanisms by which low oxygen levels influence cell functions and cellular signaling systems. Detailed information is still lacking about the location and mechanism of most hypoxic-mediated alterations in cell signaling pathways. However, information about how factors altered by trauma and sepsis, such as Po2, acidosis, and endotoxin, effect cellular signaling pathways is rapidly emerging. Understanding the mechanism by which oxygen availability alters cell function will be important to the development of optimal therapies for post-traumatic shock and organ dysfunction.

Animals↗
PubMed1995

RNA polymerase II C-terminal domain required for enhancer-driven transcription.

The RNA polymerase II carboxy-terminal domain (CTD) consists of tandem repeats of the sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser. The CTD may participate in activated transcription through interaction with a high-molecular-weight mediator complex. Such a role would be consistent with observations that some genes are preferentially sensitive to CTD mutations. Here we investigate the function of the mouse RNA polymerase CTD in enhancer-driven transcription. Transcription by alpha-amanitin-resistant CTD-deletion mutants was tested by transient transfection of tissue culture cells in the presence of alpha-amanitin in order to inhibit endogenous RNA polymerase II. Removal of most of the CTD abolishes transcriptional activation by all enhancers tested, whereas transcription from promoters driven by Sp1, a factor that typically activates housekeeping genes from positions proximal to the initiation sites, is not affected. These findings show that the CTD is essential in mediating 'enhancer'-type activation of mammalian transcription.

Amanitins↗
PubMed1995

Independent signal transduction pathways for IL-1 and TNF in LPS-tolerant macrophages.

Macrophages rendered "tolerant" by pretreatment with low-dose endotoxin (LPSp) release less TNF and more IL-1 in response to a second activating endotoxin exposure (LPSa). We hypothesized that LPSp pretreatment alters signal transduction pathways for TNF and IL-1 independently. The effect of pretreatment with LPSp alone was compared to pretreatment with LPSp plus defined second-messenger pathway agonists or antagonists. Murine peritoneal macrophages were pretreated in vitro for 4 hr with LPSp or PMA or LPSp plus protein kinase C inhibitor (PKCi) or 8-bromo-cAMP. Cells were then washed and cultured with medium alone for 20 hr. Macrophages were also pretreated with LPSp plus indomethacin for the total 24-hr pretreatment interval. Cells were then stimulated for 24 hr with LPSa, after which supernatant TNF and IL-1 were measured by bioassay. In the absence of LPSp, mediators were increased by LPSa in a dose-dependent manner. LPSp pretreatment inhibited TNF and augmented IL-1 in response to LPSa. Pretreatment with PMA partially reproduced LPSp pretreatment. Pretreatment with PKCi alone increased both TNF and IL-1 release by LPSa. The combination of LPSp plus PKCi pretreatment further enhanced IL-1 release without affecting TNF inhibition. The addition of indomethacin had a similar effect. The combination of LPSp plus 8-bromo-cAMP blocked the augmentation of IL-1 without changing TNF inhibition. Macrophage endotoxin tolerance following LPSp pretreatment alters LPSa-triggered TNF and IL-1 release by independent signal transduction pathways.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Efficacy of radioprotective agents in preventing small and large bowel radiation injury.

PURPOSE: A variety of adjuvant treatments and cytoprotective agents have been proposed to lessen the toxicity of radiation therapy. The following study was designed to evaluate the benefit of six agents or combinations using anastomotic bursting strength as a measure of transmural radiation injury. METHODS: The 40-Gy study consisted of the following. Seventy-two male Sprague-Dawley rats were divided into eight equal groups: nonradiated control, radiated untreated control, and six radiated treated groups. The radioprotective treatments included ribose-cysteine (Rib-Cys), WR-2721, glutamine, vitamin E, MgCl2/adenosine triphosphate, and RibCys/glutamine in combination. Radiated animals received 40 Gy to the abdomen. Two weeks after radiation, all animals underwent small bowel and colonic resection with primary anastomosis. Animals were sacrificed one week postoperatively, at which time anastomoses were evaluated and bursting strengths determined. The 70-Gy study consisted of the following. The same protocol was repeated for five groups of nine rats divided into nonradiated, radiated untreated, and three radiated treated groups receiving RibCys (8 mmol/kg), RibCys (20 mmol/kg), and WR-2721. All radiated animals received 70-Gy doses. RESULTS: In the 40-Gy group, there were 10 radiation-related deaths and 6 anastomotic leaks among 70 rats studied. None of the differences between groups were significant. Nonradiated control group small bowel and large bowel anastomotic bursting pressures were significantly elevated compared with all radiated groups. Compared with radiated controls, there were significant improvements in small bowel bursting strength in the RibCys, WR-2721, RibCys-glutamine, and vitamin E groups and significant improvement in colonic bursting strength in MgCl2/adenosine triphosphate, WR-2721, and RibCys groups. In the 70-Gy group, all nine nonradiated control rats survived. All eight untreated radiated control rats died, four of eight WR-2721 animals died (P = 0.03), all RibCys (8 mmol/kg) animals died (P = 0.03), and three of nine treated with RibCys (20 mmol/kg) survived (P = 0.08). CONCLUSIONS: WR-2721 and RibCys gave consistent protection against large and small bowel radiation injury. The lower incidence of treatment-related toxicity and potentially equal or greater radioprotective effects may make RibCys more clinically useful than WR-2721.

Adenosine Triphosphate↗
PubMed1995

Sexual preference for child and aggressive stimuli: comparison of rapists and child molesters using auditory and visual stimuli.

154 Ss were tested using penile plethysmography as part of intake into a voluntary inpatient sex offender treatment program. The testing protocol included slide stimuli of nude males and females in four age categories ranging from age 1 to adult; audiotaped descriptions of sexual activity with children of both genders which included fondling, sexual contact with no resistance, coercive sexual contact, sexual assault, nonsexual assault, and consensual sexual contact with an adult; videotaped depictions of rape of an adult woman, nonsexual assault of an adult woman and consensual sexual involvement with an adult woman, and audiotaped descriptions that paralleled the videotapes. The results indicated that child molesters (male victim) show a decidedly more offense related arousal profile than either child molesters (female victim) or rapists, and that the profiles of child molesters (female victim) and rapists are remarkably similar, although statistically significantly different from each other. Rapists respond significantly more to rape and nonsexual assault than either of the two child molester groups, with child molesters with female victims responding more than those with male victims. In all three groups, the highest level of noncoercive adult responding was to women, with differences among offense groups present for visual stimuli, but not in response to auditory stimuli. Overall, the patterns of results are similar whether they are based on composites across stimulus modality or on the individual stimuli.

Acoustic Stimulation↗
PubMed1995

Malignancy, mortality, and medicosurgical management of Clostridium septicum infection.

BACKGROUND: Necrotizing Clostridium septicum infections (CSI) have a strong association with malignancy or immunosuppression. To clarify this relationship and determine how it impacted mortality, the experience with CSI at a single institution was reviewed. METHODS: Records of all patients admitted to our hospital with culture proven clostridial infection from 1966 through 1993 were reviewed. RESULTS: Among patients presenting with clinical gas gangrene, 281 had culture proven clostridial infection and 32 (11.4%) had CSI. The mortality among CSI patients was 56%, whereas 26% of all patients with clostridial infections died (p = 0.001). An associated malignancy was found in 50% of patients with CSI, whereas this was seen in only 11% of patients with other clostridial infections (p = 0.0001 for CSI versus clostridial infection overall). The remaining patients with spontaneous CSI all had evidence of immunosuppression. CONCLUSIONS: The high mortality and likelihood of associated malignancy or hematologic disease underscore the importance of a high index of suspicion and the need to search for and treat associated conditions in all patients with CSI.

Adenocarcinoma↗
PubMed1995

Mechanisms of reprogrammed macrophage endotoxin signal transduction after lipopolysaccharide pretreatment.

BACKGROUND: Dysregulation of macrophage tumor necrosis factor (TNF) and interleukin-(IL-1) release results from repetitive lipopolysacharride (LPS) stimulation. In this study we investigated the mechanisms of LPS pretreatment (LPSp) signal transduction producing altered LPS-activated (LPSa) cytokine release. METHODS: Murine macrophages were treated with medium alone, actinomycin D, cycloheximide, a protein kinase C inhibitor (H7), or the nitric oxide synthase inhibitor L-NMA. Macrophages were then pretreated with 100 ng/ml LPSp and cultured in medium alone, a nitric oxide donor (sodium nitroprusside), or a cyclic adenosine monophosphate donor (8 bromoadenosine) for 20 hours. Cultures were then washed, and fresh medium containing 1 microgram/ml LPSa was added. TNF and IL-1 release in 24-hour supernatant was measured by bioassays. RESULTS: LPSp inhibited TNF and enhanced IL-1 release. The results with actinomycin D and cycloheximide suggested that LPSp effects did not require transcription, but IL-1 enhancement required protein synthesis. Addition of 8-bromo-cyclic adenosine monophosphate, H7, or nitroprusside prevented LPSp-induced augmentation of IL-1 but had no effect on inhibition of TNF release. Inhibition of LPSp-induced nitric oxide production with L-NMA had no effect on TNF or IL-1. CONCLUSIONS: Complex, independent, but incompletely understood signal transduction pathways for LPSp-induced alterations in LPSa-stimulated macrophage TNF and IL-1 release were shown. Understanding altered signal transduction from prior LPS stimulation may suggest new therapies to control dysregulated macrophage cytokine release in sepsis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Reprogrammed macrophage tumor necrosis factor and interleukin-1 release with inflammatory pretreatment: differential regulation by endotoxin and zymosan.

OBJECTIVE: To determine whether different reprogrammed alterations in endotoxin (lipopolysaccharide, LPS)-stimulated tumor necrosis factor (TNF) and interleukin-1 (IL-1) release are seen following pretreatment with endotoxin (LPSp) or pretreatment with the particulate inflammatory stimulus zymosan. METHODS: Murine peritoneal macrophages (M phi) pretreated for 24 hours in vitro with medium, LPSp, zymosan, latex beads, or killed Escherichia coli. After 24 hours M phi were restimulated with medium, LPSa, zymosan, latex beads, or E. coli, M phi supernatant TNF and IL-1 were measured after 24 hours and mRNA levels determined after 6 hours with reverse-transcriptase polymerase chain reaction. RESULTS: Pretreatment with low dose LPSp markedly inhibited TNF release by both LPSa or zymosan, while pretreatment with zymosan increased LPSa-stimulated TNF release. Pretreatment with both LPSp and zymosan augmented LPSa and zymosan-stimulated IL-1. Zymosan pretreatment augmentation of TNF and IL-1 was accompanied by lower than basal levels of cytokine message. CONCLUSION: Reprogrammed macrophage TNF and IL-1 release was differentially regulated by distinct inflammatory stimuli. Understanding reprogrammed macrophage cytokine regulation may enable specific therapy to modify dysregulated cytokine release during sepsis and trauma.

Animals↗
PubMed1995

Endotoxin pretreatment of human monocytes alters subsequent endotoxin-triggered release of inflammatory mediators.

In trauma or sepsis, monocytes and macrophages release mediators such as tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), and prostaglandin E2 (PGE2). Although patients may be exposed to more than one stimulus, the effect of repetitive endotoxin (LPS) stimulation on human monocytes is poorly characterized. Human peripheral blood monocytes obtained from healthy volunteers were pretreated with endotoxin (LPS1) for 24 h. Cultures were then restimulated for 24 h with a second, activating LPS stimulus (LPS2) at various concentrations and supernatant mediators (TNF, IL-1, IL-6, and PGE2) measured. Serum cytokine levels of normal monocyte donors were compared to basal and LPS-stimulated cytokine release of their monocytes in vitro. LPS2 increased all mediators in a dose-dependent manner in the absence of LPS1 pretreatment. LPS1 significantly increased LPS2-triggered monocyte secretion of IL-1, IL-6, and PGE2, but inhibited TNF release. Cell-associated TNF and IL-1 were also inhibited and enhanced in parallel with supernatant levels of the respective cytokines. Serum cytokine levels were low, showed wide variation, and correlated poorly with in vitro LPS-triggered cytokine production. Human monocyte mediator production is differentially regulated by endotoxin pretreatment. Provocative in vitro testing of monocytes could identify prior LPS exposure and may be more useful than serum cytokine measurements.

Adult↗
PubMed1994

Antigen processing and class II MHC peptide-loading compartments in human B-lymphoblastoid cells.

The peptide/class II major histocompatibility complex (MHC) complexes recognized by CD4+ T cells have been characterized at the structural and biochemical levels and studies on the transport and maturation of class II MHC indicate that specialized sites may be involved in peptide acquisition. Here we report the characterization of the compartments involved in antigen processing and class II MHC loading relative to distinct functional domains of the endocytic pathway in antigen-specific human B lymphocytes. Peroxidase-mediated crosslinking analysis in intact cells demonstrates that peptide loading of class II MHC takes place in a compartment accessible to membrane immunoglobulin but not to transferrin receptors, although processing may be initiated within the latter domain. The density of membrane vesicles carrying newly assembled class II MHC complexes was distinct from early and late endosomes and dense lysosomes. Endocytosed antigen-gold complexes enter a class II MHC-rich compartment morphologically very similar to that described previously and within the time frame of biochemically detectable peptide loading.

B-Lymphocytes↗
PubMed1994

Macrophage endotoxin tolerance. Tumor necrosis factor and interleukin-1 regulation by lipopolysaccharide pretreatment.

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.

Animals↗
PubMed1994

Macrophage endotoxin tolerance: effect of TNF or endotoxin pretreatment.

Macrophages pretreated with low-dose endotoxin [lipopolysaccharide (LPS1)] have an altered response to subsequent endotoxin (LPS2) stimulation, a process known as endotoxin tolerance. In this study we investigated whether the LPS1 pretreatment effects were mediated primarily via tumor necrosis factor (TNF alpha). Murine peritoneal macrophages were pretreated in vitro with either TNF alpha or LPS1 and the effects on mediator production in response to a second endotoxin exposure, LPS2, were compared. Mediators in macrophage supernatant were measured using specific bioassays [TNF, interleukin-1 (IL-1), and IL-6] or enzymatic immunoassays [prostaglandin E2 (PGE2) and TNF]. Macrophage production of all mediators was stimulated by endotoxin in the absence of LPS1 pretreatment. Pretreatment with LPS1 completely inhibited LPS2-triggered TNF release whereas preexposure to TNF alpha had no effect. In contrast, LPS1 pretreatment significantly augmented IL-1 and PGE2 release in response to LPS2, whereas pretreatment using either high- or low dose TNF alpha did not. TNF, stimulated by an initial exposure to endotoxin, LPS1, is not solely responsible for the observed alterations in macrophage mediator release following a subsequent endotoxin stimulus (LPS2). Thus, the data suggest that endotoxin tolerance is mediated primarily by factors other than TNF.

Animals↗
PubMed1994

The relationship between treatment goals and recidivism among child molesters.

Preliminary findings from a longitudinal outcome study of sex offender treatment are presented. Ss included 76 child molesters who were treated in a comprehensive relapse prevention program, and 79 molesters who were randomly assigned to a control (no treatment) condition. Three sets of findings are reported: survival analyses of time to reoffense; in-treatment change data relevant to the program's treatment goals; and the relationships between treatment measures and risk of reoffense. Over an average followup period of 38 months, there was a trend for treatment Ss to be at lower risk for both sex and violent crimes than were controls. Treatment Ss showed significant progress towards treatment goals of increased acceptance of personal responsibility for their crimes and decreased levels of deviant sexual arousal. Measures of personal responsibility, however, were not related to risk of rearrest for new sex crimes. Treatment Ss with high levels of both deviant and nondeviant sexual arousal were more likely to commit new sex offenses, but not other violent offenses. The strongest predictor in the study was a measure of the Ss' skills in applying the relapse prevention model, with highly skilled Ss being less likely to commit new sex crimes.

Adaptation, Psychological↗
PubMed1994

Pre-exposure to hypoxia or septic stimuli differentially regulates endotoxin release of tumor necrosis factor, interleukin-6, interleukin-1, prostaglandin E2, nitric oxide, and superoxide by macrophages.

UNLABELLED: Shock states with resulting inadequate cellular oxygen delivery may contribute to macrophage (M phi) activation or dysregulation. In this study we compared the effects of transient anoxia and endotoxin pretreatment (LPS1) on M phi mediator release with a second endotoxin stimulus (LPS2). METHODS: In vitro cultures of murine peritoneal exudate M phi were exposed to 2 hours of hypoxic or normoxic conditions, then incubated 22 hours under identical normoxic conditions +/- 10 ng/mL of LPS1 pretreatment. During the final 24 hours all M phis were exposed to a range of LPS2 concentrations. The M phi supernatants were assayed for tumor necrosis factor (TNF), interleukin 1 (IL-1), interleukin 6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO), and superoxide release. RESULTS: LPS1 markedly inhibited M phi TNF release by LPS2, but hypoxia had no effect on LPS2-triggered TNF release. Hypoxia increased M phi IL-6 production in the absence of LPS1, but inhibited the LPS1 augmentation seen under normoxic conditions. Pretreatment with LPS1 increased NO production from LPS2 under normoxic conditions, but hypoxia inhibited this effect. Superoxide production increased by LPS1 under normoxic conditions, but hypoxia significantly inhibited superoxide release. CONCLUSIONS: The effects of transient anoxic exposure on LPS2-triggered M phi function are markedly different from the effects of pretreatment with septic stimuli (LPS1).

Analysis of Variance↗