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D G Remick

Publications and source records attributed to D G Remick.

At least 55 records · Page 3Linked to original sources
PubMed1997

Regulation of platelet-activating factor receptor gene expression in vivo by endotoxin, platelet-activating factor and endogenous tumour necrosis factor.

A competitive PCR assay was developed to quantify platelet-activating factor (PAF) receptor (PAF-R) transcripts in rat tissues using a synthetic RNA as a competitor. We found PAF-R mRNA constitutively expressed in the eight organs tested, with the ileum containing the highest concentration [(3.49+/-0.15) x 10(7) molecules/microg of RNA]. Significant but lower levels were also detected in the jejunum, spleen, lungs, kidneys, heart, stomach and liver. Furthermore we defined the regulatory role of inflammatory mediators in ileal PAF-R gene expression using a rat model of intestinal injury induced by PAF or lipopolysaccharide (LPS). Injection of LPS or low-dose PAF resulted in a marked increase in ileal PAF-R mRNA within 30 min. The up-regulation on PAF-R elicited by PAF was biphasic, peaking first at 90 min, then again at 6 h. In contrast, LPS elicited a weak monophasic response. The second phase of PAF-R mRNA increase after PAF administration was completely abolished by WEB 2170, a PAF antagonist, and partially inhibited by antitumour necrosis factor (TNF) antibody. These observations indicate the involvement of endogenous PAF and TNF in this event. In conclusion, we found: (a) preferential PAF-R expression in the ileum, suggesting a role for PAF in intestinal inflammation; (b) induction of PAF-R expression in vivo by its own agonist; (c) a complex regulation of PAR-R gene expression in vivo involving a network of various pro-inflammatory mediators.

Animals↗
PubMed1997

Cytokine responses of human blood monocytes stimulated with Igs.

Using an in vitro system for stimulating human peripheral blood mononuclear cells (PBMC) with immobilized Ig, patterns of cytokine production as a function of different Ig classes and subclasses were elucidated. Wells were coated with IgA, IgG1, IgG2, IgG3 or IgG4. Equivalent protein content on surfaces of wells was demonstrated by a human kappa chain ELISA. Isolated human PBMC were added to Ig-coated wells and incubated for 24 hrs before supernatants were assayed for cytokines. The IgG subclasses showed differences in cytokine production stimulated from PBMC, with the relative stimulation for TNF alpha being IgG2 > or = IgG3 > or = IgG1 > IgG4 and for IL-6 production, IgG2 > or = IgG3 > IgG1 = IgG4. In contrast, the relative stimulation for IL-8 was IgG1 = IgG2 = IgG3 = IgG4. IgA caused less production of TNF alpha when compared to IgG2, but similar levels of IL-8. Such differences may have important implications in the pathogenesis of immune complex mediated diseases.

Animals↗
PubMed1997

Nitric oxide regulation of interleukin-8 gene expression.

While the regulation of nitric oxide (NO) by inflammatory cytokines or lipopolysaccharide (LPS) has received considerable attention, NO modulation of cytokine expression has yet to be fully explored. The NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), inhibited interleukin (IL)-8 and IL-6 production in LPS-stimulated human whole blood in a dose-dependent manner. In the presence of 1 microgram/mL LPS, L-NAME blocked IL-8 release (72 +/- 4% inhibition at 20 mM (mean +/- SEM, p < .05)) 24 h post-LPS without affecting cellular viability. IL-6 production was significantly inhibited only with the highest dose of L-NAME used. L-NAME inhibition of IL-8 production was also observed at the mRNA level. Conversely, direct exposure of whole blood to NO with the spontaneous NO liberator DETA NONOate caused a dose-dependent stimulation of IL-8, but had no effect on IL-6 release. IL-8 concentrations rose from 8.3 +/- 1.9 ng/mL at 24 h to 31.7 +/- 7.6 ng/mL at 72 h with a single stimulation of 10 mM DETA NONOate. The hydroxyl radical scavenger dimethyl sulfoxide (DMSO) prevented the DETA NONOate induction of IL-8, suggesting the participation of the hydroxyl radical in the NO-induced IL-8 production. These results provide important evidence substantiating a role for NO as a regulator of cytokine expression.

Blotting, Northern↗
PubMed1997

The role of Legionella pneumophila-infected Hartmannella vermiformis as an infectious particle in a murine model of Legionnaire's disease.

Legionella pneumophila is a bacterial parasite of many species of freshwater protozoa and occasionally an intracellular pathogen of humans. While protozoa are known to play a key role in the persistence of L. pneumophila in the environment, there has been limited research addressing the potential role of L. pneumophila-infected protozoa in the pathogenesis of human infection. In this report, the potential role of an L. pneumophila-infected amoeba as an infectious particle in replicative L. pneumophila lung infection was investigated in vivo with the amoeba Hartmannella vermiformis, a natural reservoir of L. pneumophila in the environment. L. pneumophila-infected H. vermiformis organisms were prepared by coculture of the amoebae and virulent L. pneumophila cells in vitro. A/J mice, which are susceptible to replicative L. pneumophila lung infection, were subsequently inoculated intratracheally with L. pneumophila-infected H. vermiformis organisms (10(6) amoebae containing 10(5) bacteria), and intrapulmonary growth of the bacteria was assessed. A/J mice inoculated intratracheally with L. pneumophila-infected H. vermiformis organisms developed replicative L. pneumophila lung infections. Furthermore, L. pneumophila-infected H. vermiformis organisms were more pathogenic than an equivalent number of bacteria or a coinoculum of L. pneumophila cells and uninfected amoebae. These results demonstrate that L. pneumophila-infected amoebae are infectious particles in replicative L. pneumophila infections in vivo and support the hypothesis that inhaled protozoa may serve as cofactors in the pathogenesis of pulmonary disease induced by inhaled respiratory pathogens.

Animals↗
PubMed1997

Platelet-activating factor (PAF) up-regulates plasma and tissue PAF-acetylhydrolase activity in the rat: effect of cycloheximide.

Platelet-activating factor (PAF) is a proinflammatory phospholipid mediator implicated in necrotizing enterocolitis. Regulation of PAF-acetylhydrolase (AH), the enzyme degrading PAF, is poorly understood. In this study we found that administration of a dose of PAF (1.5 microg/kg, i.v.), which does not cause gross intestinal injury, increased plasma and intestinal PAF-AH in the rat. Cycloheximide (CHX, 5 mg/kg, i.v.) reduced the activity of plasma (but not intestinal tissue) AH in control, as well as in PAF-injected rats, and aggravated systemic inflammation and tissue injury in the latter. The intestinal necrosis induced by PAF and CHX was ameliorated by posttreatment with WEB2170 (a PAF antagonist), indicating a role of endogenous PAF in mediating injury. Both WEB2170 and anti-TNF antibody reduced PAF-induced AH activity in intestinal tissue, but not in the plasma. Allopurinol largely prevented the injury induced by PAF and CHX, but had no effect on the up-regulation of AH. We conclude: 1) de novo protein synthesis is required to maintain physiologic AH level in the plasma; 2) PAF up-regulates plasma and intestinal AH activity; 3) CHX enhances the injurious effect of PAF; 4) endogenous PAF and TNF also play a role in the up-regulation of intestinal AH; the former probably mediating the intestinal injury by PAF; and 5) reactive oxygen species may mediate the injurious effect of PAF plus CHX, but do not contribute to the regulation of AH by PAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Regulatory effects of interleukin-6 in immunoglobulin G immune-complex-induced lung injury.

Interleukin-6 (IL-6) is a cytokine produced in response to a variety of inflammatory stimuli. Although IL-6 is often observed in increased amounts in acute respiratory distress syndrome, its role in the development of lung injury is unclear. The role of IL-6 was studied in the rat model of lung injury induced by the intra-alveolar deposition of IgG immune complexes. IL-6 induction, as determined by Northern blot analysis and bioactivity, was found as a function of time during the course of development of injury. Recombinant IL-6 instilled intratracheally at commencement of injury led to substantial reductions in lung vascular permeability, neutrophil accumulation, and levels of tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2 in bronchoalveolar lavage fluids. Conversely, blocking of intrinsic IL-6 by a neutralizing antibody resulted in increases in lung vascular permeability, neutrophil content, and TNF-alpha levels in bronchoalveolar lavage fluids. Rat alveolar macrophages stimulated in vitro with lipopolysaccharide in the presence of IL-6 showed a significant reduction in TNF-alpha expression. Together, these findings suggest that IL-6 acts as an intrinsic regulator of lung inflammatory injury after deposition of IgG immune complexes and that the protective effects of exogenously administered IL-6 may be in part linked to suppressed TNF-alpha production.

Animals↗
PubMed1996

Humoral immunity and regulation of intrapulmonary growth of Legionella pneumophila in the immunocompetent host.

The potential role of humoral immunity in regulating intrapulmonary growth of Legionella pneumophila in the immunocompetent host was investigated using a murine model of Legionnaires' disease. Intratracheal inoculation of A/J mice with a virulent strain of L. pneumophila (10(6) bacteria per mouse) resulted in the recruitment of B lymphocytes into the lung and the development of anti-L. pneumophila Ab. Opsonization of L. pneumophila in vitro with anti-L. pneumophila-specific mAb resulted in a significant decrease in intrapulmonary growth of the bacteria at 24 to 72 h postinfection. Transmission electron microscopic analysis of lung tissue from L. pneumophila- infected mice demonstrated that while there was no significant difference between phagocytosis of the unopsonized and opsonized L. pneumophila by alveolar macrophages at 24 h postinfection, phagocytosis of opsonized bacteria by alveolar mononuclear phagocytic cells was significantly enhanced at 48 h postinfection. Depletion of A/J mice of complement before intratracheal inoculation of opsonized L. pneumophila (10(6) bacteria per mouse) did not significantly alter intrapulmonary growth of L. pneumophila. These results suggest that anti-L. pneumophila Ab, produced during replicative L. pneumophila lung infections, may regulate intrapulmonary growth of L. pneumophila in the immunocompetent host by decreasing the viability of extracellular L. pneumophila and by enhancing phagocytosis of the bacteria by alveolar mononuclear phagocytic cells by a complement-independent mechanism.

Animals↗
PubMed1996

Tumor necrosis factor-alpha and FMLP receptors are functionally linked during FMLP-stimulated activation of adherent human neutrophils.

Human peripheral blood neutrophils (PMN) plated onto fibrinogen and activated with FMLP release H2O2 and lactoferrin, a specific granule component, with parallel kinetics. Although tumor necrosis factor-alpha (TNF alpha) only primes PMN in suspension, it is a potent agonist of adherent PMN. Activation of adherent PMN by FMLP (10(-7) mol/L) stimulated detectable release of TNF alpha within 45 minutes of stimulation, with maximal release (45.5 pg/10(6) cells) detected by 90 minutes. TNF alpha release paralleled the release of both lactoferrin and H2O2. To determine if TNF alpha plays a role in H2O2 and lactoferrin release, we investigated the effect of anti-TNF alpha antibodies on FMLP-stimulated activation of adherent PMN. A neutralizing rabbit anti-TNF alpha antibody inhibited both H2O2 and lactoferrin release stimulated by FMLP, whereas rabbit lgG, anti-HLA-A,B,C, anti-CD 14, and anti-interleukin-8 antibodies were without effect. The simultaneous addition of TNF alpha (1,000 U/mL) with anti-TNF alpha antibody reversed the inhibition seen with anti-TNF alpha alone. Furthermore, treatment of PMN with either actinomycin D or cylcoheximide resulted in partial (33%) inhibition of H2O2 and lactoferrin release, suggesting that protein synthesis is required for FMLP-mediated activation of adherent PMN. The addition of TNF alpha to either cycloheximide or of actinomycin D-treated PMN overcame the inhibition, indicating that the effect was specific for TNF alpha. The addition of antibodies against either the 55-or 75-kD TNF alpha receptors (referred to as p55 and p75, respectively) resulted in partial (32%) inhibition of FMLP-mediated activation of H2O2 and lactoferrin release, whereas a combination of both antibodies reduced their release to control levels. These data indicate that both p55 and p75 are involved in FMLP activation of adherent PMN. Taken together, these findings indicate that the production of TNF alpha and ligation of TNF alpha receptors are central to FMLP activation of PMN adherent to fibrinogen.

Animals↗
PubMed1996

TNF-alpha potentiates oxidant and reperfusion-induced endothelial cell injury.

Pulmonary edema following reperfusion is a major clinical problem. Changes in endothelial cell shape induced by oxidant injury may account for immediate capillary leakage associated with reperfusion injury. In these experiments we examined the role of tumor necrosis factor-alpha (TNF-alpha) in acute endothelial cell injury following ischemia-reperfusion. Sprague-Dawley rats were treated with a neutralizing antisera directed against TNF-alpha prior to production of distal ischemia. These rats demonstrated a significant reduction (P < 0.05) in acute lung edema in response to 4 hr of ischemia and 30 min of reperfusion when compared to rats undergoing the same procedure without antisera treatment. An in vitro model was developed to determine if TNF-alpha had a direct effect on endothelial cell response to ischemia-reperfusion. The effects of TNF-alpha and oxidant stress on the integrity of cultured endothelial cell monolayers was measured. Rat pulmonary artery endothelial cell monolayers reacted in vitro to oxidant stress by an increase in permeability. The cells changed shape and an increase in diffusion of 125I-albumin across cell monolayers resulted when these cells were exposed to 50 microM hydrogen peroxide (H2O2) or plasma from the ischemic hind limb of a Sprague-Dawley rat (50 microliters/ml). Pretreatment of cultured cells with low levels of recombinant mouse TNF-alpha significantly affected both the cell shape change and the increase in permeability (P < 0.05). Increased permeability of cell monolayers in vitro was not due to cell lysis as determined by media lactate dehydrogenase levels. The effect appeared to be due to cellular rounding and contraction seen using video time lapse microscopy. These data suggest a direct effect of TNF-alpha on endothelial cells, whereby the cells are rendered more susceptible to oxidant injury accompanying reperfusion.

Acute Disease↗
PubMed1996

Regulation of cytokine gene expression by reactive oxygen and reactive nitrogen intermediates.

Reactive oxygen intermediates (ROI), reactive nitrogen intermediates (RNI), and cytokines are frequent companions at sites of acute inflammation. Previous work has established a clear link between the production of cytokines and the subsequent generation of ROI and RNI. However, more recent data indicates that ROI and RNI not only serve as end-stage effector molecules of pathogen destruction and tissue injury, but also as initiators of acute inflammation. Specifically, ROI and RNI will upregulate cytokine gene expression since antioxidants inhibit interleukin 8 (IL-8) production and do not decrease production of other cytokines. Treatment with hydroxyl radical scavengers such as dimethyl sulfoxide (DMSO) will decrease the production of IL-8 in stimulated human whole blood, fibroblasts, type II epithelial cells, and hepatoma cells, but not other cytokines. Addition of exogenous ROI will increase IL-8 production in these same cells. Inhibition of nitric oxide synthase will decrease production of IL-8, whereas addition of nitric oxide (NO)-generating compounds will increase production of IL-8. The hydroxyl radical appears to be the final common pathway of cell activation for IL-8 synthesis, since DMSO will inhibit the NO-driven production of IL-8. Our data indicate that ROI and RNI can serve as intracellular second messengers to induce IL-8 gene expression.

Animals↗
PubMed1996

Radiation-induced lung injury in vivo: expression of transforming growth factor-beta precedes fibrosis.

Cytokine release from irradiated cells has been postulated to start soon after irradiation preceding detectable clinical and pathological manifestation of lung injury. The expression of transforming growth factor beta (TGF beta), a fibrogenic and radiation-inducible cytokine, was studied from 1-16 weeks after the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation caused an increase in TGF beta protein in bronchoalveolar lavage (BAL) fluid peaking at 3-6 weeks as compared to sham-irradiated control rats. Steady state TGF beta mRNA expression as shown by whole lung northern blot assay paralleled the TGF beta protein expression in BAL fluid. The peak of TGF beta protein increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8-10 weeks after irradiation. In conclusion. TGF beta and mRNA and protein upregulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis.

Animals↗
PubMed1996

The intratracheal administration of endotoxin: X. Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo.

Intratracheal instillation of endotoxin (LPS) causes acute pulmonary inflammation characterized by the accumulation of plasma proteins and leukocytes within the pulmonary airways. The synthetic glucocorticoid dexamethasone 1) inhibits the LPS-initiated vascular leak of plasma proteins into the airspace, 2) inhibits the LPS-initiated emigration of neutrophils and lymphocytes into the airspace in a dose-dependent fashion, and 3) inhibits LPS-initiated mRNA and/or bronchoalveolar lavage protein expression of cytokines (TNF, IL-1 and IL-6) and chemokines (MIP-1 alpha, MIP-2 and MCP-1). In conclusion, dexamethasone inhibits both the vascular and cellular aspects of acute inflammation by downregulation of a broad spectrum of inflammatory cytokines and chemokines.

Animals↗
PubMed1996

RANTES in onchocerciasis: changes with ivermectin treatment.

Adverse reactions are seen relatively frequently after treatment of onchocerciasis patients with ivermectin. The chemokines RANTES and IL-8, which have both chemotactic and activation properties for eosinophils and neutrophils, respectively, may have a role in the pathogenesis of post-treatment reactions. Circulating levels of the chemokines and the cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-6 were measured in the plasma of 22 Onchocerca volvulus-infected subjects. Peaks of mean circulating levels of RANTES and TNF-alpha were seen at 6 h after ivermectin administration. Peripheral eosinophil counts declined at 36 h post-treatment and an early peak in RANTES levels was associated with a delay in peripheral eosinopenia. RANTES levels were negatively correlated with severity of rash (P < 0.001) and lymphoedema (P < 0.05), suggesting that high circulating levels of RANTES may inhibit eosinophil sequestration. No changes in circulating levels of IL-8 were seen. These findings suggest a possible role of circulating RANTES in modulating eosinophil sequestration in vivo.

Adolescent↗
PubMed1996

Pentoxifylline fails to prevent the Jarisch-Herxheimer reaction or associated cytokine release.

The Jarisch-Herxheimer reaction (JHR) observed after antibiotic treatment of relapsing fever caused by Borrelia recurrentis is associated with the systemic appearance of cytokines. The decrease of cytokine production and block of JHR was attempted by administering pentoxifylline prior to antibiotic treatment. Fifteen patients with confirmed relapsing fever were infused intravenously with pentoxifylline 90 min before intramuscular injection of penicillin; 4 patients were not treated with pentoxifylline. All patients developed JHR to varying degrees. Treatment with pentoxifylline failed to prevent fever, increase in pulse, respiration, or blood pressure, or decrease in white blood cell count. No reduction of circulating levels of tumor necrosis factor, interleukin 6, or interleukin-8 was observed with pentoxifylline treatment. Pentoxifylline did not prevent clearance of the B. recurrentis spirochetes. Thus, pentoxifylline treatment of patients with relapsing fever fails to prevent or diminish JHR or the associated cytokine release observed after appropriate antibiotic treatment.

Adolescent↗
PubMed1996

Plasma proinflammatory cytokine concentrations, Acute Physiology and Chronic Health Evaluation (APACHE) III scores and survival in patients in an intensive care unit.

OBJECTIVE: To more clearly define the relationships between plasma proinflammatory cytokine concentrations, physiologic disturbance, and survival in severely ill patients. DESIGN: Prospective, longitudinal, cohort analytic study. SETTING: Teaching hospital intensive care unit (ICU). PATIENTS: Two hundred fifty-one consecutive nonselected patients admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily Acute Physiology and Chronic Health Evaluation (APACHE) III scores were calculated from clinical and laboratory data. In concurrent blood samples, plasma concentrations were measured of four proinflammatory cytokines (tumor necrosis factor-[TNF] alpha, interleukin [IL]-1 beta, IL-6, and IL-8), all of which are believed to be of central importance in host proinflammatory and immune responses. Plasma TNF concentrations were increased in 42 patients, plasma IL-1 beta in 15 patients, IL-6 in 194 patients, and IL-8 in 52 patients at presentation. Although admission plasma IL-1 beta, IL-6, and IL-8 concentrations were higher in patients who died in the ICU compared with survivors (n = 33; p < .02, p < .01, p < .02, respectively), only admission plasma IL-8 concentrations were higher in patients with a fatal outcome if all in-hospital deaths were considered (n = 53; p = .05). APACHE III score was the best predictor of mortality (odds ratio 11.41; p = .003). Detection, but not the absolute level, of TNF bioactivity in plasma was a weak independent predictor of death (odds ratio 3.17; p = .02). There was no relationship between bacteremia or presence of the systemic inflammatory response syndrome and plasma cytokine concentrations. Nineteen patients were in the ICU for > or = 10 days, and of these 19 patients, 16 patients had prolonged increases of plasma cytokines. Two patients with persistently increased plasma TNF concentrations died. Otherwise, persistently increased plasma cytokine concentrations had a variable relation to daily APACHE scores and to mortality. CONCLUSIONS: Plasma cytokine concentrations fluctuate in serious illness and have a poor correlation with derangement of whole body physiology in seriously ill patients. Only the presence of bioactive TNF in plasma was an independent predictor of mortality. Daily measurement of plasma proinflammatory cytokine concentrations is unlikely to have clinical application in the ICU setting, except possibly in specific subgroups of patients.

APACHE↗
PubMed1996

Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by intratracheal or intravenous challenge with Corynebacterium parvum in sensitized rats.

Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations.

Alveolitis, Extrinsic Allergic↗
PubMed1996

Transcriptional and post-transcriptional regulation of interleukin-8.

Steady-state mRNA for interleukin (IL) 8 persists significantly longer than mRNA for tumor necrosis factor (TNF)-alpha in lipopolysaccharide (LPS) stimulated human whole blood. Nuclear run-ons demonstrated consistent levels of transcriptional activity of the IL-8 gene at 2 and 26 hours after LPS stimulation when compared with the rapid induction and arrest of the TNF-alpha gene. Inhibition of cellular transcription with actinomycin D added at 2 hours after LPS resulted in the substantial decrease of both IL-8 and TNF-alpha mRNAs, demonstrating half-lives of 4.6 and 2.3 hours, respectively. In contrast, inhibition of transcription at 23 hours after LPS revealed extremely stable IL-8 mRNA with a half-life of > 10 hours. The half-life of beta-actin in the same actinomycin-D-treated samples did not vary significantly from the half-life calculated at the 2-hour time point (5.5 hours versus 5.6 hours), indicating that the observed IL-8 mRNA stability was not an artifact of the system. Both IL-8 and TNF-alpha protein levels decreased when actinomycin D was added 2 hours after LPS stimulation. However, no effect in IL-8 protein levels was evident when actinomycin D was added at 23 hours after LPS. These results demonstrate that IL-8 mRNA stability is controlled at both the transcriptional and posttranscriptional levels of gene regulation.

Humans↗