Biomedical subjects

D G Remick

Publications and source records attributed to D G Remick.

At least 37 records · Page 2Linked to original sources

PubMed2000

Kupffer cell activation by lipopolysaccharide in rats: role for lipopolysaccharide binding protein and toll-like receptor 4.

Lipopolysaccharide (LPS) binding protein (LBP) is a key serum factor that mediates LPS activation of mononuclear cells. In the presence of LBP, 1/1,000 the concentration of LPS is sufficient to activate peripheral blood monocytes. Previous studies with Kupffer cells have shown a variable effect of serum on LPS activation of these cells and led to the conclusion that, unlike extrahepatic mononuclear cells, Kupffer cells do not respond to LPS in an LBP-dependent fashion. Because there are multiple components in serum other than LBP that might affect LPS activation, these reports with serum are difficult to interpret. To investigate the specific role of LBP in LPS activation of Kupffer cells, we produced a functional recombinant rat LBP using a baculovirus expression system, which we used to selectively examine the role of LBP's on Kupffer-cell function. Isolated Kupffer cells exposed to increasing concentrations of LPS (0, 1, 10 ng/mL) showed a dose-dependent increase in TNF-alpha production, which was augmented and accelerated by the presence of LBP. The effects of LBP on Kupffer cell activation by LPS are dependent on a functional Toll-like receptor 4 (Tlr 4) because Kupffer cells from C3H/HeJ mice failed to respond to LPS in the presence of LBP. LBP plays an important role in mediating Kupffer cell activation by LPS, and these effects are dependent on the presence of functioning Tlr 4.

Acute-Phase Proteins↗

PubMed2000

Recombinant human interleukin-10 fails to alter proinflammatory cytokine production or physiologic changes associated with the Jarisch-Herxheimer reaction.

Interleukin (IL)-10 may have a role in the treatment of cytokine-associated inflammatory syndromes. The Jarisch-Herxheimer reaction (J-HR), which follows antibiotic treatment of Borrelia recurrentis infection, is a useful model of acute systemic inflammation associated with a cytokine surge and characteristic pathophysiologic changes. In a double-blind, placebo-controlled study, 49 Ethiopian men with B. recurrentis infection were randomized to receive a single intravenous bolus of either 25 microg/kg of recombinant human (rh) IL-10 or vehicle control shortly before receiving intramuscular penicillin. Patients were monitored for physiologic changes, and plasma samples were taken repeatedly for 24 h after treatment. rhIL-10 had no impact on changes in any of the physiologic parameters of J-HR, plasma cytokine levels, or the rate of spirochete clearance. A single intravenous bolus of 25 microgram/kg of rhIL-10 does not seem to have a useful role in the treatment of the J-HR associated with B. recurrentis infection.

Adolescent↗

PubMed2000

Comparison of the mortality and inflammatory response of two models of sepsis: lipopolysaccharide vs. cecal ligation and puncture.

Sepsis remains a serious clinical problem despite intense efforts to improve survival. Experimental animal models of sepsis have responded dramatically to immunotherapy blocking the activity of cytokines. Despite these preclinical successes, human clinical trials have not demonstrated any improvement in survival. We directly compared the mortality, morbidity, and immunopathology in two models of sepsis, one due to lipopolysaccharide (LPS) and the other to cecal ligation and puncture (CLP). BALB/c mice were injected intraperitoneally with 250 microg of LPS or subjected to CLP with an 18-gauge needle. Both models yielded similar mortality (> 85%) and morbidity. Additionally, neutropenia and lymphopenia developed in both groups. Plasma and peritoneal levels of cytokines (TNF, IL-1, IL-6, and the chemokines KC and MIP-2) were measured at 1.5, 4, and 8 h after challenge. LPS induced substantially higher levels of cytokines in both compartments with peak levels between 1.5 and 4 h that began to decline at 8 h. In contrast, cytokine levels in the CLP model were continuing to increase at the 8 h-time point and often exceeded the LPS-induced values at this time. Our data demonstrate that the LPS and CLP models have similar mortality but significant differences in the kinetics and magnitude of cytokine production. Immunotherapy for sepsis based on cytokine production after LPS challenge is misdirected because the LPS model does not accurately reproduce the cytokine profile of sepsis.

Animals↗

PubMed2000

Immunopathology of a two-hit murine model of acid aspiration lung injury.

In a two-hit model of acid aspiration lung injury, mice were subjected to nonlethal cecal ligation and puncture (CLP). After 48 h, intratracheal (IT) acid was administered, and mice were killed at several time points. Recruitment of neutrophils in response to acid was documented by myeloperoxidase assay and neutrophil counts in bronchoalveolar lavage (BAL) fluid and peaked at 8 h post-IT injection. Albumin in BAL fluid, an indicator of lung injury, also peaked at 8 h. When the contributions of the two hits were compared, neutrophil recruitment and lung injury occurred in response to acid but were not greatly influenced by addition of another hit. Neutrophil sequestration was preceded by elevations in KC and macrophage inflammatory protein-2alpha in plasma and BAL fluid. KC levels in BAL fluid were higher and peaked earlier than macrophage inflammatory protein-2alpha levels. When KC was blocked with specific antiserum, neutrophil recruitment was significantly reduced, whereas albumin in BAL fluid was not affected. In conclusion, murine KC mediated neutrophil recruitment but not lung injury in a two-hit model of aspiration lung injury.

Acids↗

PubMed2000

Cytokines and the brain: implications for clinical psychiatry.

OBJECTIVE: This article reviews recent developments in cytokine biology that are relevant to clinical psychiatry. METHOD: The authors reviewed English-language literature of the last 15 years that pertains to the biology of cytokines with emphasis on central nervous system effects in general and psychiatric disorders in particular. RESULTS: Growing evidence suggests that, in addition to providing communication between immune cells, specific cytokines play a role in signaling the brain to produce neurochemical, neuroendocrine, neuroimmune, and behavioral changes. This signaling may be part of a generalized, comprehensive mechanism to mobilize resources in the face of physical and/or psychological stress and to maintain homeostasis. The clinical implications of these findings are far-reaching and include a possible role for cytokines in the pathophysiology of specific psychiatric disorders such as major depression, schizophrenia, and Alzheimer's disease. The effects of cytokines in the central nervous system may provide a possible mechanism for the "sickness behavior" of patients with severe infection or cancer, as well as for the neuropsychiatric adverse effects of treatment with interferons and interleukins. CONCLUSIONS: A better understanding of the role of cytokines in various brain activities will enhance knowledge of specific psychobiological mechanisms in health and disease and provide opportunities for novel treatment interventions.

Brain↗

PubMed1999

Neutrophil sequestration in liver and lung is differentially regulated by C-X-C chemokines during experimental peritonitis.

C-X-C chemokines play an important role in the migration and activation of neutrophils (PMNs) during an inflammatory event. We measured mRNA and protein expression of the murine C-X-C chemokines macrophage inflammatory protein-2 (MIP-2) and KC in the lungs, liver, blood, and peritoneal cavity of Swiss Webster mice after cecal ligation and puncture (CLP). Neutralizing antibodies to MIP-2 and KC were also used to determine the biological effects of these chemokines on neutrophil sequestration and organ injury in the CLP model. The data showed that early after CLP, MIP-2 mRNA and protein were expressed predominantly by the lung, whereas KC mRNA and protein were expressed by the liver. Inhibition of MIP-2 reduced both lung neutrophil sequestration and peritoneal neutrophil migration. Inhibition of KC had no effect on overall neutrophil sequestration in liver but reduced injury as measured by serum transaminases. An early survival benefit was found with anti-KC treatment, although overall survival was not different. Our study showed a differential expression by organs of C-X-C chemokines during sepsis and suggested that such chemokine effects are tissue-specific.

Animals↗

PubMed1999

Immunopathologic responses to non-lethal sepsis.

Although sepsis causes significant morbidity and mortality, its basic pathology is still not well understood. We investigated the inflammatory and physiologic alterations of non-lethal sepsis using cecal ligation and puncture (CLP), a model that induces peritonitis due to mixed intestinal flora, reproducing the complex immunology of sepsis. Groups of mice were subjected to CLP (25G needle) or sham surgery, had minimitters implanted to continuously monitor temperature and activity, and were sacrificed daily for 6 days. There was significant hypothermia (6-13 hrs post-surgery), and decreases in activity (to day 4) and weight (to day 3) but no mortality in the CLP group. Blood analyses of the CLP-treated mice showed reduced hemoglobin, platelets, lymphocytes, monocytes, and neutrophils, compared to sham animals. Both groups had nearly equivalent neutrophil influx into the peritoneum. Plasma and peritoneal G-CSF, IL-6, as well as the murine chemokines KC and MIP2-alpha were significantly higher in the CLP-treated mice at day 1. Plasma and peritoneal TNF were low (<70 pg/mL). While there was elevated IL-1beta in the peritoneum of the CLP-treated mice, this cytokine was not detected in the plasma in either treatment group. Cytokines were not detected in the pulmonary airspace of the CLP-treated mice and PMNs were not recruited to this site. Our data shows altered immunopathology in non-lethal sepsis with significant blood and cytokine alterations. Since there was 100% survival, the inflammatory response was appropriate and probably even protective.

Animals↗

PubMed1999

Childhood asthma.

Asthma prevalence in children has increased 58% since 1980. Mortality has increased by 78%. The burden of the disease is most acute in urban areas and racial/ethnic minority populations. Hospitalization and morbidity rates for nonwhites are more than twice those for whites. Asthma is characterized by recurrent wheezing, breathlessness, chest tightness, and coughing. Research in the past decade has revealed the importance of inflammation of the airways in asthma and clinical treatment to reduce chronic inflammation. Asthma is associated with production of IgE to common environmental allergens including house dust mite, animal dander, cockroach, fungal spores, and pollens. Some interventions to reduce symptoms through control of dust mite and animal dander have had positive results. Control of symptoms through interventions to reduce exposures to cockroach antigen has not been reported. Studies illustrating causal effects between outdoor air pollution and asthma prevalence are scant. Increases in asthma prevalence have occurred at the same time as general improvements in air quality. However, air quality appears to exacerbate symptoms in the child who already has the disease. Decreased pulmonary function has been associated with exposure to particulates and bronchial hyperresponsiveness to smoke, SO(2) and NO(2). Symptoms have been correlated with increased levels of respirable particulates, ozone, and SO(2). Interventions that reduce the negative outcomes in asthma associated with outdoor environmental factors have not been reported. Control of asthma in children will entail the collaborative efforts of patients, family, clinical professionals, and school personnel, as well as community-wide environmental control measures and conducive national and local policies based on sound research.

Air Pollution, Indoor↗

PubMed1999

Plasma interference in an enzyme-linked immunosorbant assay using a commercial matched antibody pair.

In this study, severe plasma interference was repeatedly documented in an IL-1ra sandwich enzyme-linked immunosorbant assay (ELISA) using a commercial matched antibody pair. Several physical and biochemical treatments were used in an attempt to alleviate this plasma effect including the following: buffer optimization, sample dilution, increasing incubation temperature, heat treatment of plasma, increasing detergent concentrations, glutaraldehyde pretreatment of the plate and the addition of polyethylene glycol (PEG). Evaluation of several buffers demonstrated that the range of optical densities could be increased dramatically with the use of an appropriate buffer. Of the treatments examined, only the addition of polyethylene glycol (PEG) to the dilution buffer created a marked improvement in the ELISA, despite a resulting background increase. Further investigation demonstrated that 10% PEG in the dilution buffer added to biotinylated antibody and the streptavidin provided the greatest improvement to the sensitivity of the ELISA.

Antibodies↗

PubMed1999

Venovenous modified ultrafiltration after cardiopulmonary bypass in children: a prospective randomized study.

BACKGROUND: Cardiopulmonary bypass is associated with the production of both proinflammatory and anti-inflammatory cytokines, the balance of which leads to varying degrees of postoperative systemic inflammation. Arteriovenous modified ultrafiltration effectively reduces total body water and improves postoperative hemodynamic and homeostatic functions. Venovenous modified ultrafiltration is a modification of this technique, which has the potentially added advantage of eliminating the obligatory left-to-right shunt associated with arteriovenous modified ultrafiltration. We tested the hypothesis that venovenous modified ultrafiltration is a safe and effective method of achieving ultrafiltration in children after cardiopulmonary bypass. METHODS: Thirty-eight pediatric patients were randomly assigned to undergo conventional, venovenous (n = 13), or no ultrafiltration venovenous (n = 13), and controls (n = 12). Perioperative, cardiopulmonary, and cytokine (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-8, and interleukin-10) data were collected for statistical analysis. RESULTS: Compared with patients in the conventional ultrafiltration and control groups, patients undergoing venovenous modified ultrafiltration had the greatest volume of ultrafiltrate removed (46. 9 +/- 8.4 mL/kg vs 20.1 +/- 5.0 mL/kg and 0 mL/kg for conventional ultrafiltration and control groups, respectively; P =.0001), least increase in total body water (1.91% +/- 1.49% vs 3.90% +/- 1.86% and 8.24% +/- 3.41%; P =.05), greatest rise in hematocrit (39.7% +/- 1. 7% vs 33.8% +/- 2.1% and 29.6% +/- 2.3%; P =.006), and shortest length of hospital stay (4.41 +/- 0.28 days vs 6.69 +/- 1.47 days and 8.38 +/- 1.11 days; P =.03, P =.03). CONCLUSIONS: Venovenous modified ultrafiltration is a safe and effective method of reducing the increase in total body water and duration of postoperative convalescence after cardiopulmonary bypass.

Cardiopulmonary Bypass↗

PubMed1998

Blood mononuclear cell production of TNF-alpha and IL-8: engagement of different signal transduction pathways including the p42 MAP kinase pathway.

Recent studies of human peripheral blood mononuclear cells (PBMC) stimulated with IgG subclasses have suggested that tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) production proceed along different signal transduction pathways. To investigate this possibility, inhibitors of signal transduction pathways were employed. Human PBMC were pretreated with various inhibitors before being added to IgG2-coated wells and 4-h supernatant fluids evaluated for cytokine content. The effects of various inhibitors on MAP kinase activation were determined. Inhibitors of protein tyrosine kinases, phosphatases, and phospholipase C decreased TNF-alpha and IL-8 production, suggesting that all three enzyme pathways are involved in cytokine generation. Inhibitors of G-proteins had differing effects: pertussis toxin inhibited IL-8 but not TNF-alpha production, whereas cholera toxin inhibited TNF-alpha but not IL-8 production. Pretreatment of PBMC with pertussis toxin resulted in reduced IgG2-induced calcium mobilization, whereas cholera toxin had no effect, correlating with the effects of pertussis toxin on IL-8 expression. Inhibitors of protein kinase C (PKC) completely blocked TNF-alpha generation but had no effect on IL-8 production. Gö6976, which inhibits certain isoforms of PKC, inhibited production of both IL-8 and TNF-alpha. Isoforms of PKC may have opposing effects on cytokine production. PD 98059, a compound that specifically inhibits the activation of mitogen-activated protein kinase kinase (MEK1), inhibited TNF-alpha production, but had insignificant effects on IL-8 production. Pretreatment of PBMC with either PD 98059 or genistein reduced the extent of phosphorylation of p42 MAP kinase in cells activated on contact with IgG2. These findings suggest distinct signal transduction pathways for cytokine production in PBMC stimulated with IgG2.

Calcium↗

PubMed1998

Tissue coexpression of LBP and CD14 mRNA in a mouse model of sepsis.

BACKGROUND: Lipopolysaccharide binding protein (LBP) markedly increases the sensitivity of immune cells to LPS and CD14 expression correlates with cellular responsiveness to LPS. LBP gene expression can be induced in multiple organs following injury and CD14 upregulation on monocytes correlates with the infection and mortality rates in severely injured patients. We sought to determine the time-course induction of LBP and CD14 gene expression following experimental peritonitis. MATERIAL AND METHODS: BALB/c mice were subjected to laparotomy alone or laparotomy with cecal ligation and puncture and treated with Imipenem. At serial time points, animals were sacrificed and tissues harvested for isolation of RNA and protein. LBP, CD14, and cytokine mRNAs were analyzed by Northern blot analysis and TaqMan fluorescent quantitative RT-PCR. RESULTS: LBP and CD14 mRNA levels were significantly increased in all three organs from CLP mice compared to sham-operated mice. IL-1 mRNA levels increased in all three organs following CLP with significantly higher levels found in the lungs compared to the kidney and liver. No significant differences were noted in local TNF mRNA levels. CONCLUSIONS: LBP, CD14, and IL-1 mRNA levels are induced concurrently in the lung, kidney, and liver after cecal ligation and puncture. Given the synergistic affect of LBP and CD14 in potentiating LPS-induced production of inflammatory cytokines and the hypothesized role of such cytokines in the etiology of MSOF following injury and sepsis, our findings suggest a mechanism by which these organs may be rendered more susceptible to a "second hit" from endotoxemia after initial injury.

Acute Disease↗

PubMed1998

Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 secretion and the acute-phase response in patients with bacterial and tuberculous osteomyelitis.

Osteomyelitis, or bone infection, is a major worldwide cause of morbidity. Treatment is frequently unsatisfactory, yet little is known about pathogenesis of infection. Plasma tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 concentrations were measured before and after lipopolysaccharide stimulation of whole blood from patients with bacterial and tuberculous osteomyelitis and from controls. Patients with bacterial and tuberculous osteomyelitis mounted an acute-phase response and were anemic and febrile. However, plasma IL-6 concentrations were significantly elevated in only tuberculous osteomyelitis patients (vs. controls, P < .05). IL-6 concentrations correlated with erythrocyte sedimentation rate, C-reactive protein level, and plasma albumin concentration, all acute-phase markers. There were no other correlations between cytokine concentrations and clinical data. Following ex vivo stimulation, TNF, IL-6, and IL-8 were secreted equally by patients and controls. In summary, tuberculous osteomyelitis is characterized by elevated systemic IL-6 concentrations associated with an acute-phase response. For further insight into immunopathology of osteomyelitis, studies on infected bone are required.

Acute-Phase Reaction↗

PubMed1998

Exogenous interleukin-10 fails to decrease the mortality or morbidity of sepsis.

OBJECTIVE: To determine if exogenous interleukin (IL)-10 will decrease the morbidity or mortality of sepsis induced by cecal ligation and puncture. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Adult, female, Balb¿c mice. INTERVENTIONS: Balb¿c mice were subjected to cecal ligation and puncture with an 18- or 23-gauge needle and treated with triple antibiotics. Mice were injected subcutaneously with recombinant human IL-10 (diluted in normal saline with 0.1% mouse serum albumin) and followed until death. In a separate experiment, IL-10 was also injected subcutaneously and lipopolysaccharide (LPS) injected intraperitoneally and plasma tumor necrosis factor concentrations measured 90 mins later. MEASUREMENTS AND MAIN RESULTS: In the LPS experiments, IL-10 decreased tumor necrosis factor (TNF) production by nearly 90%. For the cecal ligation and puncture experiments, temperature and movement were recorded continuously via implanted transmitters. Studies on mortality indicated that exogenous IL-10 given at 0, +6 and +12 hrs after surgery failed to increase survival when using an 18-gauge needle (alive:total cecal ligation and puncture alone 4:21; IL-10 10 microg/mouse 2:12; 1 microg/mouse 8:25; 0.1 microg/mouse 1:12) or a 23-gauge needle (cecal ligation and puncture alone 13:29; IL-10 1 microg 18:30). There was no difference in the number of hours to death between the groups. IL-10 did not prevent the hypothermia after cecal ligation and puncture or increase the animals' activity. To examine parameters of inflammation, mice were killed 8 hrs after 18-gauge cecal ligation and puncture. IL-10 (1 microg/mL) failed to reduce pulmonary neutrophil sequestration (lung myeloperoxidase, cecal ligation and puncture 107 +/- 10 [SEM], IL-10 107 +/- 5) or recruitment of neutrophils to the peritoneum (neutrophils x 10(6), cecal ligation and puncture 3.72 +/- 0.62; IL-10 3.49 +/- 0.37). IL-10 also failed to reduce the appearance of TNF or IL-6 in the plasma or peritoneal fluid. The chemokine KC was reduced in the peritoneal fluid but not the plasma and endogenous IL-10 production was not reduced in the peritoneum. CONCLUSION: Our data indicate that exogenous IL-10 fails to improve morbidity or mortality in the clinically relevant cecal ligation and puncture model of sepsis.

Animals↗

PubMed1998

Antibiotic treatment influences outcome in murine sepsis: mediators of increased morbidity.

Different antibiotic treatments may affect the survival and physiological responses of Balb/c mice following cecal ligation and puncture (CLP). The broad spectrum imipenem (IMP) was compared with a triple antibiotic mixture of gentamicin, clindamycin, and ciprofloxacin (3AB). Control mice received injections of 5% dextrose (D5W). After CLP with a 25 gauge needle, Mini-Mitters were implanted to measure temperature and activity. Therapy began with 1 mL injections of antibiotics or D5W 2 h post-CLP and continued every 12 h for 3 days. Survival was higher in IMP mice than in 3AB or D5W mice. Starting with the injection 12 h after CLP, 3AB always induced a profound hypothermic response not observed with D5W or IMP. Nocturnal activity levels were higher in IMP mice compared with 3AB or D5W mice during the first night following CLP. To determine the cause of this hypothermic response and to further investigate the acute effects that antibiotic choice may have on murine physiology, the kinetic appearance of IL-1, IL-6, TNF, and KC as well as lipopolysaccharide (LPS), were measured in the plasma and peritoneum of mice sacrificed at 0, .5, and 1.5 h after antibiotic injection at 24 h post-CLP. Cytokine and LPS concentrations in 3AB mice were not significantly different at any of the three time points when compared with IMP or D5W mice. Our data demonstrate that antibiotic therapy consisting of 3AB produces greater morbidity and mortality compared with therapy consisting of IMP. However, the mechanism of these alterations is not due to elevated systemic levels of cytokines or LPS.

Animals↗

PubMed1998

Low molecular weight heparin is associated with greater cytokine production in a stimulated whole blood model.

Anticoagulants can influence production of cytokines in whole blood, but the effects vary depending on the type of anticoagulant and the immunological stimulus. We examined this further by anticoagulating normal blood with either unfractionated (UF) heparin or low molecular weight heparin (Fragmin) and stimulating each sample with lipopolysaccharide, zymosan A, phytohemagglutinin, immune complexes, H2O2, or RPMI. After incubating 24 h, the combination of lipopolysaccharide and Fragmin induced significantly greater concentrations of interleukin 1 (IL)-1beta (25+/-10 ng/mL; x +/- standard error), IL-8 (21+/-6), and tumor necrosis factor (TNF)alpha (.48+/-.24) compared with heparinized blood (p < .05). The combination of Fragmin and zymosan also induced significantly greater concentrations of IL-1beta (97+/-24) and TNFalpha (2.9+/-.8), but not IL-8 (2.0+/-15). Average levels of proinflammatory cytokines (IL-1beta, IL-6, IL-8, and TNFalpha) were greater with Fragmin anticoagulation for 36 of 40 comparisons, and patterns were similar for 6 h and 24 h incubations. Statistical difference was established in 33% of these comparisons. A composite score of proinflammatory cytokines for Fragmin-anticoagulated blood was significantly greater than expected for UF heparinized blood (p < .0001) after 24 h. Expression of one anti-inflammatory cytokine (IL-10) was only slightly elevated for Fragmin anticoagulation. Proinflammatory cytokines are produced in greater quantities with Fragmin anticoagulation, which may be a disadvantage for ischemic conditions (e.g., cardiac surgery) but advantageous for long-term treatment of thrombosis.

Anticoagulants↗

PubMed1998

In vivo regulation of replicative Legionella pneumophila lung infection by endogenous interleukin-12.

The in vivo role of endogenous interleukin 12 (IL-12) in modulating intrapulmonary growth of Legionella pneumophila was assessed by using a murine model of replicative L. pneumophila lung infection. Intratracheal inoculation of A/J mice with virulent bacteria (10(6) L. pneumophila cells per mouse) resulted in induction of IL-12, which preceded clearance of the bacteria from the lung. Inhibition of endogenous IL-12 activity, via administration of IL-12 neutralizing antiserum, resulted in enhanced intrapulmonary growth of the bacteria within 5 days postinfection (compared to untreated L. pneumophila-infected mice). Because IL-12 has previously been shown to modulate the expression of cytokines, including gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-10, which regulate L. pneumophila growth, immunomodulatory effects of endogenous IL-12 on intrapulmonary levels of these cytokines during replicative L. pneumophila lung infection were subsequently assessed. Results of these experiments demonstrated that TNF-alpha activity was significantly lower, while protein levels of IFN-gamma and IL-10 in the lung were similar, in L. pneumophila-infected mice administered IL-12 antiserum, compared to similarly infected untreated mice. Together, these results demonstrate that IL-12 is critical for resolution of replicative L. pneumophila lung infection and suggest that regulation of intrapulmonary growth of L. pneumophila by endogenous IL-12 is mediated, at least in part, by TNF-alpha.

Animals↗

PubMed1998

Elevated concentrations of eotaxin and interleukin-5 in human neurocysticercosis.

Symptomatic neurocysticercosis, a major cause of epilepsy worldwide, results from inflammation around Taenia solium larvae, but the mechanisms are unknown. Eotaxin, not previously reported in cases of human infection, and interleukin-5 (IL-5) but not IL-8 concentrations were elevated in patient serum, and IL-5 levels were also elevated in cerebrospinal fluid (CSF). Eosinophil-selective mediators may be involved in the pathogenesis of cysticercosis. IL-6 concentrations were also elevated in patient CSF, possibly indicative of an acute-phase response.

Adult↗