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Background: Exposure to microorganisms elicts the production of cytokines. These soluble factors enhance several innate immune functions and regulate the ensuing specific immune response aimed at limiting the spread of infection., Aim: This study was undertaken to quantify the plasma levels of pro-inflammatory cytokines during the course of primary Listeria monocytogenes and Campylobacter jejuni infection. Using an in vivo infection the relationship between endogenous cytokines and the bacterial number in the liver of infected animals was examined., Methods: C57BL/6 mice were infected by the intraperitoneal route. At different time points we determined the number of colony-forming units of bacteria in the liver of infected animals and paralled these with the plasma levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) measured by enzyme immunoassays., Results: L. monocytogenes infection lasted 10-11 days. IFN-gamma production occurred in the early phase but was more pronounced after day 4, following the appearance of specific immunity. The duration of experimental campylobacteriosis was 15 days. Early IFN-gamma production was not significant but a progressive rise of this cytokine in plasma was seen during the second week post infection. Mice produced measurable amounts of plasma TNF-alpha immediately after being given viable L. monocytogenes, peaking on day 2-3 when the greatest number of bacteria was present in the examined organs. During C. jejuni infection plasma TNF-alpha was produced in a similar manner, but the highest concentrations were found a few days later than in listeriosis, in correlation with the different course of campylobacteriosis. The quantity of IL-6 increased and decreased in concordance with clearance of L monocytogenes and the clinical status of the animals. C. jejuni did not promote the induction of this cytokine. This is to some extent an unusual finding. With respect to the role of IL-6 in Th2 responses and antibody production, the appearance of this cytokine in campylobacteriosis was more expected., Discussion: During systemic bacterial infection, a network of pro-inflammatory cytokines is activated and blood levels of these cytokines are elevated, albeit inconsistently, with large individual variations and depending on microbial characteristics and structure.

The pregnancy-associated glycoprotein (PAG) concentration profiles of goats that had been experimentally inoculated with either Toxoplasma gondii or Listeria monocytogenes are described. All goats were examined regularly by ultrasonography. In T. gondii-infected females (n = 5), a slow decrease of PAG was observed throughout a period of 55 to 74 d after inoculation. Afterwards, the goats either aborted (n = 4) or kidded 1 dead and 1 weak fetus (n = 1). In L. monocytogenes-infected females (n = 8), a marked decrease of PAG was observed from the day of inoculation. Abortion occurred within 9 to 11 d post inoculation (n = 7). Only 1 goat kidded a healthy fetus.

In this study we investigated the effects of the treatment with Chlorella vulgaris extract (CVE) on the hematopoietic response of granulocyte-macrophage colony-forming unit (CFU-GM) of mice infected with a sublethal dose of Listeria monocytogenes (1 x 10(4) organisms/animal). CVE was given orally as 50 mg/kg/day for 5 days. In the CVE treated/infected groups L. monocytogenes was administered at the end of CVE treatment. The colony stimulating activity of the serum (CSA) was also studied in all groups. Although no effects on CFU-GM, as compared to controls, were observed in the groups receiving CVE alone, the extract produced an increase in CSA levels as compared to controls. On the other hand, the presence of the infection led to a significant reduction in the numbers of CFU-GM as observed at 48 and 72 h after the infection, in spite of the significant increase in serum CSA activity. CVE treatment of infected animals restored the numbers of CFU-GM to control levels. In the treated/ infected group the increased serum CSA was significantly higher than that observed in the only infected group. The CVE treatment (50 and 500 mg/kg) of mice infected with a dose of 3 x 10(5) bacteria/animal, which was lethal for all the non-treated controls, produced a dose-response protection which led to a 20 and 52% survival, respectively. These results demonstrated that CVE produces a significant increase in the resistance of the animals infected with L. monocytogenes, and that this protection is due, at least in part, to increased CFU-GM in the bone marrow of infected animals.

Murine experimental meningitis models induced by either Escherichia coli LPS, live Streptococcus pneumoniae, or Listeria monocytogenes were used to study the origin and potential function of soluble CD14 (sCD14) in the brain during bacterial meningitis. Whereas intracerebral infection caused only a minor and/or transient increase of sCD14 levels in the serum, dramatically elevated concentrations of sCD14 were detected in the cerebrospinal fluid. Reverse-transcriptase PCR and FACS analysis of the leukocytes invading the subarachnoid compartment revealed an active amplification of CD14 transcription and concomitant surface expression. These findings were confirmed by in situ hybridization and immunohistochemical analysis. In contrast, parenchymal astrocytes and microglial cells were shown not to significantly contribute to the elevated levels of sCD14. Simultaneous intracerebral inoculation of rsCD14 and S. pneumoniae resulted in a markedly increased local cytokine response. Taken together, these data provide the first evidence that sCD14 can act as an inflammatory co-ligand in vivo. Thus, during bacterial meningitis, sCD14 is massively released by intrathecal leukocytes, and the sCD14 found in the cerebrospinal fluid can play an important role in the pathogenesis of this disease.

The heavy metal lead (Pb) has been shown to downregulate various parameters of cell-mediated immune (CMI) responses. This inhibition of CMI responses by Pb is exemplified by a higher mortality rate upon infections with sublethal doses of a variety of pathogens. Unlike Pb, which lowers host resistance, interleukin-12 (IL-12) exerts a substantial stimulatory influence on the host response to intracellular bacteria such as Listeria monocytogenes. To explore the influence of IL-12 in mice rendered susceptible to Listerial infection by oral exposure to Pb, we determined bacterial burdens and production of interferon gamma (IFN-gamma). As expected, Pb-exposed mice had increased morbidity due to higher Listerial titers as compared to control mice. However, administration of exogenous IL-12 reversed the Pb-induced inhibition of host defense and boosted the resistance of the non-Pb-treated mice. The enhanced CMI responses observed in both IL-12-treated groups were accompanied with elevations of IFN-gamma in the sera and spleens. Significant reduction in the number of viable Listeria in Pb-exposed mice upon IL-12 administration suggests that the processes downstream of IL-12 production were intact in the Pb-exposed mice and that the inhibition by Pb was due to the lack of functional IL-12. Alternatively, the exogenous IL-12 may have overcome a downstream effect by enhancing an secondary pathway. Support for the former hypothesis is based on the observation that Pb induced elevated levels of p40 splenic messenger RNA since increased p40 expression would result from lack of IL-12 formation. Contrary to the IFN-gamma levels, significantly higher levels of IL-6 and corticosterone were observed in the sera and spleens of Pb-exposed mice upon infection, suggesting heightened stress in the absence of IL-12. Overall, the results suggest that an environmental pollutant such as Pb can enhance the stress response, which naturally occurs during an infection, and can further compromise health by lowering host resistance by altering cytokine levels.

The influence of L. monocytogenes on the hemopoietic system was studied in mouse experiments. All elements of hemopoiesis were damaged. The most pronounced changes developed in erythropoiesis. This was testified by a decrease in erythrocyte count and hemoglobin content in peripheral blood, by the hypoplasia of the hemopoietic erythroid germ in the marrow, as well as by the decrease of yield in culture CFU-E. These changes in the hemopoietic tissue supposedly caused by the direct action of L. monocytogenes and its toxins.

A nested PCR-based test was developed for the detection of Listeria monocytogenes in blood specimens from patients with listeriosis. Two pairs of oligonucleotide primers were designed to amplify a 1395-bp and a 453-bp fragment of the iap gene of L. monocytogenes. Amplified products were analysed with gel electrophoresis and stained with ethidium bromide. The PCR method described could be routinely used to diagnose listeriosis.

A case of congenital Listeria septicemia is reported. A 2256 g male infant suffering from respiratory and circulatory failure with shock-like symptoms and high levels of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, -6, and -8), was admitted to the Morioka Red Cross Hospital. Listeria monocytogenes was cultured from cord blood, contents from the external ear canal, rectum and stomach. The infant was treated with surfactant replacement as well as conventional therapy. The high levels of interleukin-1 beta decreased with the improvement of the circulatory function, which might have been the major cause of the poor clinical state.

Experimental infections were induced with different bacterial forms of Listeria monocytogenes: parental (S-forms), protoplastic (L-forms) and combined inoculum of both forms by i.p. injection of rats. The parental bacterial forms (S-forms) were isolated up to 7 days after challenge from the peritoneal cavity and the liver, while the L-forms were isolated up to 60 days from the peritoneal cavity. Continuous adhesion of L-forms on the peritoneal macrophage surface was found by scanning-electron microscopy. Erythrocyte and leucocyte count as well as some clinical chemistry parameters were measured during infections. They showed different dynamics in the three experimental groups. Histomorphological changes in the liver (microabscesses and mononuclear cellular granulomas) of infected animals were observed. They were less intensive and appeared later in rats infected with L-forms. The experiments demonstrated that infections caused by parental bacterial forms and by combined inoculum took an acute course, while the infection caused by L-forms could be distinguished as a prolonged and persistent one.

The authors report a case of Listeria monocytogenes septicemia in a patient with advanced CLL after a single course of fludarabine, without any other immunosuppressive therapy e.g. corticosteroids. The immunosuppressive action of fludarabine in patients who are already severely immunosuppressed must be considered from a diagnostic and therapeutic point of view. Listeriosis and other opportunistic infections, like pneumocystis carinii pneumonia, have been reported during and after treatment with purine analogues. Prophylaxis with cotrimoxazole must therefore be discussed in patients with CLL treated with fludarabine.

Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens, and also mediates cation-independent macrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from MSR-A-deficient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defence against pathogens.

Plasma from eight newborns (4 pre-term and 4 full-term) with early-onset (< 72 h) sepsis and six apparently healthy controls was analyzed. The presence of spots identified as haptoglobin and serum amyloid A protein was the electrophoretic result most consistently associated with disease. Time course monitoring showed rises, peaks and declines of spot intensity as expected for acute-phase proteins induced by transient stimuli. Haptoglobin beta chains appear to be undersialated in pre-term newborns, whereas post-translational modifications of alpha chains and serum amyloid A protein are similar to those observed in adults. The undersialation of beta chain and occurrence of alpha chain phenotypes different from those found in maternal serum indicate that perinatal haptoglobin originates from neonatal synthesis.

A dot-blot assay and an enzyme-linked immunosorbent assay (ELISA) to detect listeriosis in dairy cattle were developed that detected anti-listeriolysin O antibodies in the serum of cows experimentally infected with Listeria monocytogenes. The tests utilized purified listeriolysin O (LLO) as the detection antigen and streptolysin O (SLO) to absorb cross-reacting antibodies. The two tests were compared with an agglutination test that used formalin-killed whole L. monocytogenes cells. Blood samples were collected periodically from 17 cows after intramammary gland infection, and the development of anti-LLO antibodies was followed by an agglutination test, the dot-blot test, and the ELISA. In general, an agglutination titer of > 640 was needed for a positive dot-blot anti-LLO test for nonpregnant cows. However, 1 pregnant cow with an agglutination titer of 20 was positive in the dot-blot test. The ELISA was as sensitive as the dot-blot assay but gave a quantitative measurement to distinguish serum samples of positive reactors from cross-reactors. The specificity of the LLO-based tests was further evaluated using serum from cows that had been experimentally infected with Staphylococcus aureus, 17 of which had agglutination titers for L. monocytogenes > 640. These elevated agglutination titers were probably due to cross-reacting bacterial antigens because serum from 9 of 17 of these animals did not react to the purified LLO antigen. A positive response to the LLO-based dot-blot and ELISA assays is indicative of previous or current infection with L. monocytogenes.

Reactive nitrogen intermediates (RNI), e.g., nitric oxide derived from a terminal guanido nitrogen atom of L-arginine, exhibit potent antimicrobial activity in vitro. The function of these intermediates in host defenses in vivo, however, is presently unclear. Experiments were undertaken to determine the role of RNI in the resolution of primary listerial infections of the liver. Serum RNI levels were elevated significantly in mice infected with Listeria monocytogenes. Moreover, a marked increase in RNI production was found in cultures of the parenchymal, as well as the nonparenchymal, liver cells obtained from Listeria-infected mice. RNI did not kill Listeria treated directly, however, nor were they a factor in the listericidal activity exhibited by hepatic cells. Rather, the elevated production of RNI during primary infection appeared to promote the replication of Listeria in vivo. Mice administered NG-monomethyl-L-arginine, a competitive inhibitor of RNI production, exhibited a 10- and a 100-fold reduction in the number of Listeria in their lives on days 3 and 7 postinfection, respectively. In vitro, NG-monomethyl-L-arginine stimulated the Ag-specific proliferation of T lymphocytes derived from Listeria-infected mice at concentrations that inhibited RNI production. These latter findings suggest that the elevated production of RNI during primary listerial infections suppresses host defenses by diminishing the proliferation and, consequently, the biologic response of immune cell populations.

We analysed two of our own and 21 patients described in the literature with listeria brainstem encephalitis. The disease was characterised by a prodromal state with fever, nausea and headache followed by severe brainstem dysfunction with multiple cranial nerve palsies, ataxia, respiratory insufficiency and coma. The diagnosis was established by isolation of Listeria monocytogenes from CSF and/or serum. Serological tests are without diagnostic evidence. Cerebrospinal fluid examination may not initially point to a bacterial infection. Computed tomography and magnetic resonance imaging technique might supply evidence of brainstem involvement and contribute to an early diagnosis. There is a high percentage of lethal outcome without early antibiotic therapy.

The antibody response in patients with Listeria monocytogenes septicemia and/or meningitis was investigated using Western blot analysis (WBA). Protein antigen preparations were produced from two strains of Listeria monocytogenes, representing serogroup 1 and 4, by sonication and differential centrifugation. IgG antibodies from 8 (50%) of 16 patients with culture verified septicemia and/or meningitis due to Listeria monocytogenes reacted with a 93 kDa antigen from serogroup 1, in contrast to IgG antibodies from only 1 (2%) of 51 controls; these controls represented 21 patients with infections caused by other bacteria and 30 apparently healthy blood donors. Furthermore, IgM antibodies from 3 (19%) of the patients with listeric infections bound to a 106 kDa protein antigen in contrast to none of the controls. In 3 (33%) of 9 patients from whom acute and convalescence serum were available, the patients responded by producing antibodies against new protein antigens. Current methods used in routine serological investigations, i.e. complement fixation and O-agglutination tests, were positive in only 4 (24%) of the 16 patients with listeriosis. The results point to the possibility of designing new immunoassays for detection of septicemia and meningitis caused by Listeria monocytogenes.

In order to study the epidemiology of listeriosis from 1967-1988 in Scotland, various sources of data were examined. These included reports by laboratories, reference laboratory records, hospital death and discharge records, death certificates and hospital laboratory records. Cases were reported from 13 of Scotland's 15 Health Boards. Case ascertainment via laboratory reports to the Communicable Diseases (Scotland) Unit was validated in two Health Boards. A total of 198 cases was identified with an overall attack rate which increased from 0.5 per million in 1967-1971 to 7.0 per million in 1987-1988. Feto-maternal cases were the commonest (64%). Of all cases, 33% were neonates; 53% presented with bacteraemia and 41% with meningitis. The predominant serovar of Listeria monocytogenes was 4b.

Treatment with human recombinant tumour necrosis factor-alpha (rTNF alpha) significantly enhanced resistance to Listeria monocytogenes infection in mice. The level of protection (which was dose-dependent and maximal at approximately 1.0 microgram per mouse) was similar to that previously reported for the monokine rIL-1 alpha, although somewhat greater amounts of rTNF alpha than rIL-1 alpha were required. Combined administration of suboptimal concentrations of rTNF alpha and rIL-1 alpha resulted in significant enhancement of resistance beyond that obtained with either monokine alone, whereas further increases in anti-listeria resistance were not observed at doses of rTNF alpha or IL-1 alpha that were themselves capable of inducing substantial protection. Combined administration of rTNF alpha and rIL-1 alpha was associated with a delay in onset and lessening in severity of the lymphopenia that accompanied L. monocytogenes infection. The reduced bacterial burden in the spleens and livers of mice treated with rTNF alpha and rIL-1 alpha was associated with a more rapid decline in serum colony-stimulating activity. Peritoneal macrophages from rTNF alpha- and rIL-1 alpha-treated listeria-infected mice did not demonstrate enhanced anti-listeria activity in vitro. These results provide further evidence for the potential benefits of rTNF alpha and other cytokines in promoting anti-bacterial resistance. They further suggest that use of combinations of cytokines is a strategy worthy of further consideration.

Listeria strains of different virulence were injected intravenously into rabbits of both sexes (2-4 kg). The infectious dose was 10(8) cells/kg. Blood samples were taken from the ear wein one day and immediately before the infection, then 3 h, 1, 2, 3, 6 and 10 days after it. Total white blood cell counts and their changes were determined and the number of lysosomal granules in neutrophils were counted. A marked monocytic reaction was observed after the injection of virulent Listeria monocytogenes 18 and 87/5467, partly virulent Listeria ivanovii, non-pathogenic Listeria seeligeri 87/5626 and 87/5575, and Listeria murrayi G44 strains. A late slow growth was provoked by Listeria innocua C644 and a very slight reaction by Listeria welshimeri 1830 strains. There was no change after injection of L. innocua strain 10. The number of lysosomal granules decreased significantly and remained at a low level for 6 days after the infection of L. monocytogenes strain 18 and for 3 days after the injection of L. innocua strain 10.

Transitory age-associated deficiency of the granulocyte cationic proteins as a cause of a phagocytosis disturbance, loss of the phagocyte cell ability to kill phagocytosed bacteria is established. Quantitative indexes of myeloperoxidase content, elastase and catepsin G in the neutrophil granulocytes of newborns and laboratory animals are determined. Hypothesis is developed on the transitory age-associated immunodeficiencies of the neutrophil granulocyte system as one of the endogenic risk factors in the development of infectious diseases during early postnatal period.

Early diagnosis is of great importance to improve the prognosis of septicemia. Traditional laboratory tests are either delayed like blood cultures, or unspecific like WBC count or ESR. In this retrospective pilot study we have assayed plasma cortisol, blood sugar and serum tumor necrosis factor (TNF) from patients with verified septicemia. With the approach used in this study none of the tests were able to differentiate between septicemia and other infectious febrile illnesses, or to predict if the causing organism was gram-positive or gram-negative.

A relationship between esterase positive and esterase negative lymphocytes in peripheral blood of a homogenous group of one-year old healthy bulls of NCB breed was found. Average values of other hematologic indices in these animals were also determined. Then the same indices were examined in bulls experimentally infected with Listeria monocytogenes and compared with the data for healthy animals. The following representative average values were found: erythrocytes 7,2 mill/mm3, leukocytes 8,6 thous./mm3. The proportional composition of leukocytes is: neutrophils - 33,9; eosinophils - 2,9; basophils - 0,8; monocytes - 5,5; lymphocytes - 56,9 including esterase positive cells - 74,7% and esterase negative cells - 25,3% in it. Statistically significant differences concerned the proportional composition of esterase positive and esterase negative lymphocytes, as well as the quantity of monocytes, basophils, eosinophils and that of erythrocytes and leukocytes.

Lower respiratory tract and systemic cell-mediated immunity have been studied in rabbits after infection with Listeria monocytogenes or Diplococcus pneumoniae. Respiratory tract cell-mediated immunity was evaluated by direct and indirect assays of migration inhibitory factor (MIF) production. Systemic delayed hypersensitivity was determined by means of intradermal testing with appropriate antigens. Aerosol exposure to listeria was followed by markedly increased numbers of free lower respiratory tract cells. These cells manifested antigen-stimulated inhibition of migration (mean inhibition of migration = 30.4%). Pneumococcal pneumonia was associated with similar but less dramatic changes. Intravenous administration of organisms was uncommonly followed by inhibition of lower respiratory tract cells in direct migration assays. Fractionated MIF, as well as crude supernates of antigen-stimulated lower respiratory tract and lymph node lymphocytes from animals exposed to listeria aerosols, caused inhibition of normal alveolar macrophage migration. MIF, produced by lymph node lymphocytes, has a molecular weight of approximately 65,000 and is inactivated by chymotrypsin or neuraminidase. Delayed dermal hypersensitivity to listeria antigen was observed in 54 of 55 animals exposed to listeria aerosols and in all 9 animals infected by the intravenous route. Delayed dermal reactions to pneumococcal sonicate antigen (but not capsular polysaccharide) followed D. pneumoniae respiratory tract infection in 19 of 28 animals, and was elicited in 5 of 6 animals after intravenous infection. Both local (macrophage migration inhibition) and systemic delayed hypersensitivity followed bacterial infection of the lower respiratory tract. MIF activity was shown to be one mechanism for inhibition of alveolar macrophage migration.

Eight cases of materno-fetal listeriosis were discovered at the University Women's Hospital of Basel from May 1977 until June 1980. This represent an incidence of 0,15% of all births. This infectious disease has often a fatal course for the unborn child, therefore it is important to know the clinical manifestations occurring with it. Listeriosis during pregnancy has a typical-two-stage course: During the first phase we see commonly a flu-like illness abating rapidly, about two weeks later fever starts again and premature contractions ensue, but no therapy is successful in controlling the fever and the premature labour. The usual fate for the unborn child is stillbirth or premature delivery with subsequent neonatal death due to prematurity, RDS, sepsis and meningitis. The low fetal and neonatal survival rate can be improved by two relatively simple measures: 1) a high index of suspicion with early diagnosis, 2) an early treatment with ampicillin either in the antepartal or neonatal stage. We review the epidemiology, the bacteriology, the serology and the histo-pathology of this relatively rare but important disease during pregnancy.

Our laboratory has previously reported that administration of murine recombinant interleukin 1 alpha (rIL-1 alpha) substantially enhanced the resistance of mice to Listeria monocytogenes infection. Other investigators have reported that gamma interferon (IFN-gamma) plays a pivotal role in antilisteria resistance. In the present study, we have defined doses of human rIL-1 alpha that enhanced the antilisteria resistance of mice. We then addressed the possibility that combined immunotherapy with rIL-1 alpha and recombinant IFN-gamma (rIFN-gamma) might result in an additive or synergistic enhancement of antibacterial resistance. Simultaneous administration of rIL-1 alpha and rIFN-gamma enhanced antilisteria resistance (at 3 days after infection) to a greater extent than did either cytokine alone, although the results did not imply a synergistic action between the two cytokines. Experiments which examined the effects of the timing of cytokine administration indicated that maximal protection was observed when rIL-1 alpha and rIFN-gamma were administered together concomitantly with the L. monocytogenes challenge. When we compared the separate and combined protective effects of rIL-1 alpha and rIFN-gamma throughout the course of a primary L. monocytogenes infection, we observed an additive effect of the two cytokines only at 3 days after challenge, the time at which the peak bacterial burden occurs in the spleens and livers of infected mice. Histopathological comparisons of livers and spleens from cytokine-treated and control listeria-infected mice verified that cytokine treatment reduced the severity of tissue damage in cytokine-treated listeria-infected mice. In an attempt to provide a potential mechanism for the protective effects of rIL-1 alpha and rIFN-gamma administration, we compared levels of colony-stimulating activity in sera from cytokine-treated and control listeria-infected mice. The highest levels of colony-stimulating activity were detected in sera from control listeria-infected mice; somewhat lower levels were found in sera from listeria-infected mice that received rIL-1 alpha and rIFN-gamma either alone or in combination.

Hematologic and histologic investigations were carried out on forty experimentally infected young ewes to which the infection was introduced through venous, intratracheal, and oral route as well as along the branches of nervus trigeminus parallel to the study of 3 control sheep, 12 albino mice, and other four young sheep that were injected with a water-extractive antigen obtained from Listeria. It was established that the leukocyte count rose in the first days following infection along with neutrophilia, lymphopenia, and monocytosis of a varying degree in the different animals, depending on the way of infection. Most indifferent with regard to the hematologic indices proved animals that were orally inoculated. With such animals there was also eosinophilia, which was lacking in the other experimental animals. Glycogen was predominantly found in the blood vessel walls, in the neutrophile leukocytes, the nervous tissue, and the necrotic foci, most likely in connection with the transportation of Listerial organisms and their toxic products. A drop up to the full disappearance of phospholipids was established as well as a rise of the ganglioside.

Murine listeriosis is a classical model for investigating mechanisms of cellular immunity, which involves interaction of macrophages and T lymphocytes. The early course of this experimental infection is under control of a limited number of genes in the murine host. In the present study, we asked whether the early efficient control of bacterial growth in the liver of resistant mice is related to the expression of a more rapid specific immune response in this organ than in susceptible mice. Therefore, we compared the frequencies of Listeria monocytogenes-reactive T cells in blood, spleen, and liver of resistant C57BL/6 and susceptible C3H/He Past mice after i.v. injection of a high dose of Listeria (9 x 10(5) CFU). T cells were titrated through their ability to locally transfer a delayed-type hypersensitivity reaction to viable L. monocytogenes, an effector function potentially relevant to the early step of protective mechanisms. We observed (1) a 9- and 4-fold increase by day 1 in the frequency of Listeria-reactive transfer units in the blood of C57BL/6 and C3H mice, respectively, (2) no increase in the number of Listeria-reactive transfer units in the spleen of 2-day infected mice of both strains, and (3) a 90-fold increase, at day 2, in the number of Listeria-reactive transfer units in the liver of resistant C57BL/6 compared with only a 9-fold increase in the liver of susceptible C3H/He. These results suggest that the ability of C57BL/6 mice to control the early bacterial growth (0 to 48 h) in their liver, may be related to a rapid influx of L. monocytogenes-reactive T lymphocytes.

Listeria monocytogenes was isolated from both the blood and the synovial fluid of a diabetic patient with a septic arthritis involving the ankle.

Immunoglobulin synthesis and secretion have been studied in the rabbit lower respiratory tract, both in the normal state and after infection with Diplococcus pneumoniae or Listeria monocytogenes. In vitro synthesis of immunoglobulin and specific antibody was assessed by incorporation of 14C-labeled amino acids into protein. Lower respiratory tract secretions and serum were analyzed for immunoglobulin and antibody against the infecting organism. Normal respiratory tract produced small quantities of immunoglobulin, most of which was IgG. After bacterial infection of the lower respiratory tract, there was a marked increase in local synthesis of immunoglobulin, especially IgG. Specific antibody of IgG class was produced in all lungs infected with listeria by the 11th day, and in lungs infected with pneumococcus by the 8th day. Secretions from all normal and infected lower respiratory tracts contained IgA and IgG. The IgA to IgG ratios in secretions of normal animals, and animals infected with listeria or pneumococcus, were 2.3, 2.5, and 2.6, respectively. Sera of animals infected with L. monocytogenes contained specific antibody of IgG class but lacked IgA antibody, whereas secretions had both IgA and IgG class antibody against listeria. Similarly, sera of animals infected with D. pneumoniae had IgG class antibody but no IgA antibody, whereas only IgA antibody was found in secretions. The evidence that locally synthesized immunoglobulin (especially IgA), including specific antibody, is secreted into the lower respiratory tract lumen is discussed. Further definition of the role of "local" antibacterial antibody in the respiratory tract is of considerable importance.

One hundred and ninety-six housed pregnant ewes were fed poor quality silage for two days. Ewes are reluctant to eat the silage and within 48 hours they became dull and developed diarrhoea and lameness. Despite treatment with antibiotics and calcium borogluconate 19 ewes died, more than 60 developed vaginal discharges and at lambing 94 ewes were barren. Six developed nervous signs and two of these died, one with lesions typical of listeric encephalitis. Post mortem lesions and the isolation of Listeria monocytogenes type 1/2 from lung, liver, spleen and kidney are described. L monocytogenes was also isolated from blood samples from live ewes. The estimated gross financial loss to the farmer was 5130 pounds or, for the flock, 26 pounds per ewe.

A newborn with fatal neonatal listeriosis developed septic shock, neutropenia, thrombocytopenia and profound hypoxaemia due to severe pulmonary hypertension. Tumour necrosis factor alpha, interleukin-1-beta and interferon-gamma serum concentrations were markedly elevated, suggesting the participation of these cytokines in the aetiopathogenesis of shock induced by Listeria monocytogenes in the neonate.

Rifampicin and rifapentine were used in the treatment of Listeria monocytogenes infections in normal mice and congenitally athymic (nude) mice. Results were compared with untreated controls and with the results obtained from a previous study of ampicillin in which this model was used. Low doses of rifampicin or rifapentine were adequate to cure normal mice. The efficacy of these antibiotic treatment schedules was lost in nude mice. Prolonged antibiotic treatment schedules with increased dosages were also unsuccessful. These studies show that rifampicin and rifapentine , two antimicrobial agents being capable of destroying intracellular bacteria, were not effective in curing the Listeria infection in mice with impaired host defenses.

C57BL/10 mice have previously been shown to be 100 times more resistant to intravenously injected Listeria monocytogenes than are BALB/c mice due to the action of a single gene, Lr. Differences in the histopathology of listeriosis in the two strains were sought. Of the tissues examined, only liver, spleen, blood, and thymus showed changes. In the liver, Listeria localized in Kupffer cells within 3 h of infection. By 24 h these cells became surrounded by neutrophilic polymorphonuclear leukocytes. After high doses of Listeria, the susceptible BALB/c mice showed many foci surrounded by few polymorphs, whereas in the resistant C57BL/10 mice there were relatively few foci surrounded by many polymorphs. By 4 days in sublethally infected mice the polymorphs in the liver of both strains were being replaced by monocytes and macrophages. Liver morphology returned to normal by 8 days postinfection. In the blood of both strains there was a rise in total lymphocyte numbers at 24 h, followed by a fall in T-lymphocytes and recovery at 5 days. C57BL/10 mice showed an early monocytic response in the blood, whereas BALB/c mice showed a polymorph leukocytosis. In the spleens of both C57BL/10 and BALB/c mice there was an early neutrophil response and red pulp hyperemia. This was followed by a dramatic lymphocyte depletion in the T-dependent periarteriolar regions in both strains beginning 2 days after infection. Absolute numbers of Thy-1(+) cells in spleen cell suspensions also fell to 10% of normal, recovering 6 to 8 days postinfection. Surface immunoglobulin-positive B-lymphocytes and Thy-1(-), immunoglobulin-negative "null" cells rose in both strains at days 4 to 5, returning to normal levels on days 10 to 12. Whether the null cells represent lymphocytes or other cell types remains unresolved. Thymus atrophy was seen in the BALB/c mice but not in C57BL/10 mice.

During a lethal murine infection with the gram-positive bacterium, Listeria monocytogenes, a factor appears in the serum that is capable of lysing certain tumor cells in vitro. The levels of this serum cytotoxic factor increase with the progression of morbidity. Neutralization of Listeria-induced cytotoxic factor activity with a monospecific antiserum to recombinant murine tumor necrosis factor (TNF) revealed that the cytotoxic factor was antigenically indistinguishable from natural TNF present in endotoxin-induced tumor necrosis serum. In contrast to a lethal infection, no TNF activity was detected in sera of mice throughout a sublethal infection. However, shortly after initiation of a sublethal infection, mice acquire a greatly enhanced capacity to produce serum TNF in response to an intravenous injection of endotoxin. Cultures of unfractionated spleen cells from mice with ongoing Listeria infections produced TNF when incubated in the absence, but not in the presence, of antibiotics. However, such antibiotic-treated cultures could be stimulated with endotoxin to produce substantially higher TNF yields than spleen cells of uninfected mice. It is also shown that intravenous infusion of anti-recombinant murine TNF IgG into sublethally infected mice results in increased Listeria proliferation in spleens and livers, and ultimately in death from an overwhelming infection.

After infection of mice with Listeria monocytogenes, elevated levels of colony-stimulating factors (CSFs) in the serum were quantitated by six different assays: ability to stimulate colony formation, the proliferation of 2 suspension of bone marrow cells (both measuring total colony-stimulating activity), a radioimmunoassay for macrophage-CSF (CSF-1), the WEHI-3B differentiation assay for granulocyte-CSF, and proliferation of 32D-c1-3 and FDC-P1 cell lines (specific for multi-CSF and either multi- or granulocyte-macrophage-CSFs, respectively). The great bulk of serum colony-stimulating activity represented macrophage- and granulocyte-CSFs, with small but measurable amounts of granulocyte-macrophage-CSF. The degree of elevation of serum CSF depended on the infecting dose used and the numbers of bacteria growing in the spleens and livers of the two mouse strains compared, i.e., L. monocytogenes-resistant C57BL/10 and susceptible BALB/cJ. The increase in serum CSFs occurred before the peak in bone marrow granulocyte-macrophage progenitors and before the reduction in bacterial numbers which follows the onset of specific cell-mediated immunity.

Human beings are frequently exposed to Listeria monocytogenes, but these microorganisms are rarely pathogenic for healthy subjects. In recent years an increase in the frequency of listeriosis has been reported, especially in patients with severe underlying diseases. In the present work the clinical, microbiological, therapeutic and prognostic characteristics of seven adult cases of listeriosis are reviewed. L. monocytogenes was isolated from blood, cerebrospinal fluid or both. Most patients had an underlying illness (one alcoholic, one diabetic, one lymphoma, and two aplastic anemia), and three of them had received immunosuppressive treatment. The disease can have different clinical presentations; the commonest forms were septicemia and acute meningitis. All patients with an underlying disease succumbed to listeriosis. A comment is made on the possibility of confusion between L. monocytogenes and other germs, and some aspects of the epidemiology of listeriosis are analyzed.

Many of the major alterations in plasma proteins characteristic of the hepatic acute phase response are regulated by IFN-beta 2/IL-6. Using a specific bioassay for IFN-beta 2/IL-6, which relies on the induction of the hepatic acute phase plasma protein alpha 1-antichymotrypsin in the human hepatoma cell line Hep3B clone 2 and its inhibition by anti-rIFN-beta 2/IL-6 antiserum, we have detected high levels of IFN-beta 2/IL-6 in the body fluids of patients with acute bacterial infections. Cerebrospinal fluid from four patients with acute bacterial meningitis (Streptococcus pneumoniae, Staphylococcus aureus, two cases of Listeria monocytogenes) all had high levels of IFN-beta 2/IL-6 (up to 500 ng/ml). Two of these patients with concomitant bacteremia had lower concentrations of IFN-beta 2/IL-6 in the serum (5 to 70 ng/ml). Three additional patients with Escherichia coli, Pseudomonas aeruginosa, and Neisseria meningitidis bacteremia had high levels of serum IFN-beta 2/IL-6, as did the ankle fluid of a patient with Streptococcus canis arthritis. Normal cerebrospinal fluid and serum had little detectable IFN-beta 2/IL-6. A combination of immunoaffinity chromatography and immunoblotting procedures were used to characterize the IFN-beta 2/IL-6 species present in a representative sampling of serum and cerebrospinal fluids. Multiple immunoreactive species of IFN-beta 2/IL-6 in the size range 23 to 30 kDa as well as immunoreactive complexes in the range 60 to 70 kDa were detected in human body fluids. This is the first demonstration that previous descriptions of heterogeneity in human IFN-beta 2/IL-6 species produced in cell culture correspond to observations in the infected host.

Estradiol, progesterone, and hydrocortisone were measured by radioimmunoassay in peripheral serum of pregnant ewes infected with Listeria monocytogenes type 5 and in normal pregnant controls. Progesterone had decreased in both groups at abortion or parturition. Estradiol and hydrocortisone of control ewes had increased at parturition. In infected ewes, the serum hydrocortisone value was high for 3 days after inoculation, but it returned to preinoculation levels for the remainder of gestation. Serum concentrations of hydrocortisone did not change, and estradiol values increased slightly at abortion by infected ewes.

The bacteria of Wellshimer's strain L. monocytogenes and their extract (LMA) showed in vitro the mitogenic activity which was demonstrated by increased proliferation of normal bone marrow cells and blood monocytes of the mouse strains resistant (C57Bl/6) and susceptible (DBA/2) to listeriosis. In the same experimental conditions the proliferation of spleen macrophages and resident peritoneal macrophages was not influenced. Besides, C57Bl/6 bone marrow cells, activated by live or killed L. monocytogenes, produced some growth factor for secondary bone marrow cell cultures.