Serum Concentrations Of Interferon-gamma Research Articles

Alterations of circulating free fatty acids in patients with pemphigus vulgaris.

Free fatty acids (FFA) have gained research interest owing to their functions in both local and systemic immune regulation. Changes in the serum levels of anti-inflammatory short chain fatty acids (SCFA), primarily derived from the gut microbiota, and pro-inflammatory medium (MCFA) and long (LCFA) chain fatty acids, derived from either the gut microbiota or the diet, have been associated with autoimmunity. Circulating FFA were retrospectively analysed by a gas chromatography-mass spectrometry method in the serum of 18 patients with pemphigus vulgaris (PV) at the baseline and 6 months (n = 10) after immunosuppressive treatments, and 18 healthy controls (HC). Circulating FFA were correlated with the Pemphigus Disease Area Index (PDAI) and serum concentrations of interferon-gamma (IFN-γ), Interleukin (IL)-17A, IL-5, IL-10 and IL-21. Principal Component analysis computed on FFA abundances revealed significant differences in the profile of SCFA (p = 0,012), MCFA (p = 0.00015) and LCFA (p = 0,035) between PV patients and HC, which were not significantly changed by immunosuppressive treatments. PV patients showed a significantly lower serum concentration of propionic (p < 0.0005) and butyric (p < 0.0005) acids, SCFA with anti-inflammatory functions, while hexanoic (p < 0.0005) and hexadecanoic (p = 0.0006) acids, pro-inflammatory MCFA and LCFA respectively, were over-represented. Treatments induced a significant decrease of hexanoic (p = 0.035) and a further increase of hexadecanoic (p = 0.046) acids. Positive correlations emerged between IFN-γ and acetic acid (Rho = 0.60), IFN-γ and hexanoic acid (Rho = 0.46), IL-5 and both hexadecanoic acid (Rho = 0.50) and octadecanoic acid (Rho = 0.53), butyric acid and PDAI (Rho = 0.53). PV was associated with a remarked imbalance of circulating FFA compared to HC. The serum alterations of SCFA, MCFA, and LCFA may contribute to promoting inflammation in PV. Deeper insights into the immunomodulatory functions of these molecules may pave the way for personalized dietary interventions in PV patients.

Comparative analysis of the anticoagulant activities and immunogenicity of HSC70 and HSC70TKD of Haemaphysalis flava

BackgroundHaemaphysalis flava is a hematophagous ectoparasite that acquires the nutrition needed for development and reproduction by sucking blood and digesting the blood meal. During blood-sucking and blood-meal digestion, the prevention of blood coagulation is important for this tick. Previous studies have shown that heat shock cognate 70 (HSC70) protein has certain anticoagulant activities, but its immunogenicity remains unclear. Also, whether the mutation of individual bases of the TKD-like peptide of HSC70 through the overlap extension method can change its anticoagulant activities and immunogenicity remains to be investigated.MethodsThe gene encoding the HSC70 protein was cloned from a complementary DNA library synthesized from H. flava. The coding gene of the TKD-like peptide of HSC70 was mutated into a TKD peptide coding gene (HSC70TKD) using the overlap extension method. Escherichia coli prokaryotic expression plasmids were constructed to obtain the recombinant proteins of HSC70 (rHSC70) and HSC70TKD (rHSC70TKD). The purified rHSC70 and rHSC70TKD were evaluated at different concentrations for anticoagulant activities using four in vitro clotting assays. Emulsifying recombinant proteins with complete and incomplete Freund’s adjuvants were subcutaneously immunized in Sprague Dawley rats. The serum antibody titers and serum concentrations of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were detected using an indirect enzyme-linked immunosorbent assay to assess the immunogenicity of rHSC70 and rHSC70TKD.ResultsThe open reading frame of HSC70 was successfully amplified and found to have a length of 1958 bp. The gene encoding the TKD-like peptide of HSC70 was artificially mutated, with the 1373-position adenine (A) of the original sequence mutated into guanine (G), the 1385-position cytosine (C) mutated into G and the 1386-position G mutated into C. rHSC70 and rHSC70TKD that fused with His-tag were obtained using the expression plasmids pET-28a-HSC70 and pET-28a-HSC70TKD, respectively. rHSC70 and rHSC70TKD prolonged the thrombin time (TT) and reduced the fibrinogen (FIB) content in the plasma, but did not affect the prothrombin time (PT) or activated partial thromboplastin time (APTT) when compared to the negative control. Interestingly, the ability of rHSC70TKD to prolong the TT and reduce the FIB content in the plasma was better than that of rHSC70. The specific antibody titers of both rHSC70 and rHSC70TKD in rat serum reached 1:124,000 14 days after the third immunization. The serum concentration of IFN-γ in the rHSC70TKD group was higher than that in the rHSC70 group. The rHSC70 group has the highest serum concentration of IL-4, and the serum concentration of IL-4 in the rHSC70TKD group was higher than that in the negative group.ConclusionsrHSC70 and rHSC70TKD exhibited anticoagulant activities by prolonging the TT and reducing the FIB content in vitro. rHSC70TKD had better anticoagulant activities than rHSC70. Both rHSC70 and rHSC70TKD had good immunogenicity and induced humoral and cellular immunity.

Changes Resulting From Resistance Training in the Ratio of Interferon-gamma to Insulin-like Growth Factor 1 and Lipid Profile in Diabetic Rats

Background and Objectives Diabetes is associated with an increase in inflammatory markers and development of atrophy and cardiovascular diseases. Studies have shown that resistance training at appropriate intensity can reduce inflammation generally. This study aims to investigate the effect of a progressive resistance training (PRT) program on serum concentrations of interferon gamma (IFN-γ), and insulin-like growth factor 1 (IGF-1) and lipid profile in rats with type 1 diabetes. Subjects and Methods In this experimental study, 32 male Wistar rats aged 40 days and weighing 250±30 g were divided into four groups of healthy control, healthy trained, diabetic control, diabetic trained. Streptozotocin (55 μg/kg per body weight) was injected intraperitoneally to induce diabetes. A 6-week PRT protocol was performed, including climbing a ladder with weights at three sessions per week (one hour per day), where the load increased by 5% increase each week. Data were analyzed by ANOVA followed by Tukey’s post hoc test. The significance level was set at 0.05. Results There was no significant difference in IFN-γ level between the diabetic trained group and other groups (P&gt;0.05). The IGF-1 level in diabetic trained group was significantly lower than in the healthy control and trained control groups (P=0.002). The ratio of IGF-1/IFN-γ in diabetic trained group was significantly lower than in the trained control (P=0.003) and healthy control (P=0.008) groups. In assessing the lipid profile, the cholesterol level was higher in the diabetic trained group compared to the healthy control group (P=0.028). Moreover, triglyceride level was significantly higher in the diabetic trained group compared to the diabetic control (P=0.033), trained control (P=0.003) and healthy control (P=0.002) groups. Conclusion Six weeks of PRT cannot lead to desired efficacy in diabetic rats compared to non-trained diabetic rats. However, the small changes such as increased IGF-1 and HDL levels and decreased serum glucose level, can help with the clinical improvement of patients with type 1 diabetes.

Inflammatory Cytokine IFNγ, IL-6, and IL-10 Association with Childhood Obesity

Abstract Childhood obesity carries a high risk of serious life-threatening cardiometabolic diseases in adulthood, which are associated with low-grade inflammation. The aim of the present study was to measure serum cytokine concentrations in obese children recruited during endocrinology consultations and compared to lean control the results. Blood serum concentrations of interferon gamma (IFNγ), IL-1β, Interleukin 6 IL-6, IL-10, and TNF-α were analysed applying Luminex xMap technology with Millipore reagent kits. Statistical analyses were performed using t-test comparisons and Spearman correlations. Obese children had highly significant increased levels of circulating IFNγ (p &lt; 0.0001), IL-6 (p &lt; 0.0001), and IL-10 (p &lt; 0.0001), compared to lean controls. IL-1β and TNFα levels, however, were not elevated. Significant correlation of serum cytokines to per cent excess body mass was only observed with IL-6 (rs = 0.21, p &lt; 0.03), although IL-1β (rs = 0.18, p &lt; 0.08) results were suggestive of a trend. A significant association of obesity in childhood with serum concentrations of IFNγ, IL-6, and IL-10 is consistent with a role for low-grade inflammatory processes early in the aetiology of this disease. IL-6 further appears to be a candidate cytokine for assessment of degree of sub-acute inflammation associated with excess weight in the young.

Characterisation of the serum cytokine profile in feline atopic skin syndrome.

Feline atopic skin syndrome (FASS) is a pruritic and inflammatory skin disease commonly encountered in cats. Three previous reports evaluated cytokine immune activation in cats diagnosed with feline allergic dermatitis. However, no significant upregulations were observed in allergic cats compared to healthy controls. To evaluate differences in the serum cytokine profile of cats diagnosed with FASS compared to healthy cats, and correlate serum markers with the extent of FASS skin disease using clinical scoring systems. Thirteen client-owned FASS cats and 12 healthy control cats. Thirteen cytokine and chemokines from the serum of FASS cats and healthy controls were analysed using a commercially available feline-specific multiplex assay. Patients with FASS had a significant increase in serum concentrations of interferon-gamma (IFN-γ), interleukin (IL)-2, IL-13 and IL-18. In addition, cytokine/chemokines involved in inflammation and chemotaxis [IL-8, C-C Motif Chemokine Ligand (CCL)5, CCL2 and CXCL12], as well as growth factors, stem cell factor and Fms-related tyrosine kinase 3 ligand (Flt3L), also were significantly elevated. A significant positive correlation (r=0.64) between the serum levels of Flt3L and Scoring Feline Allergic Dermatitis (SCORFAD) score was observed. These results demonstrate the activation of a broad array of immune secretory cytokines in the serum of cats with FASS, which are largely associated with a mixed Th1 and Th2 inflammatory response along with specific growth factors. Further larger-sample studies are needed to assess the modulation of serum biomarkers in FASS by pharmacological/therapeutic interventions.

Serum Concentrations of Interferon Gamma (IFN-γ) in Patients with Psoriasis: Correlation with Clinical Type and Severity of the Disease.

Introduction: The etiopathogenesis of psoriasis is still unclear but there is evidence that many of cytokines released by keratinocytes and inflammatory leukocytes may contribute to the induction or persistence of the inflammatory process in psoriasis. Aim: The aim of the study was to evaluate serum concentrations of Interferon gamma (IFN-γ) in patients with psoriasis and the healthy subjects and also to assess a possible association between IFN-γ, clinical type and severity of disease. Material and Methods: The study included a total of 60 patients with psoriasis and 20 healthy subjects in the control group. According to the clinical type of disease, patients with psoriasis were divided into four groups: psoriasis vulgaris (PV), psoriasis erythrodermica (PE), psoriasis pustulosa (PP) and psoriasis arthropatica (PA). Blood samples were collected from all psoriasis patients and from healthy control subjects. Serum IFN-γ levels were measured by an enzyme-linked immunosorbent assay (ELISA) technique. The severity of PV was assessed by Psoriasis Area and Severity Index (PASI) score. Results: The serum concentration of IFN-γ in patients with psoriasis was significantly higher than that in the control group (1.91±1.79 pg/mL vs 0.91±0.38 pg/mL, respectively). Significantly elevated serum IFN-γ concentrations were noticed in patients with PV (2.15±0.30 pg/mL). There was no statistically significant difference between the mean values of IFN- γ compared to the clinical type of psoriasis (p>0.05). In the group of patients with PV 36 (85.71%) patients had mild form of disease with PASI <50, and 6 (14.29%) patients had severe disease with PASI >50. It was not found statistically significant correlation between serum IFN-γ level and PASI score in the group of PV. Conclusions: The results of our study indicate that psoriasis is associated with significant changes in the serum concentration of IFN-γ. There was no significant correlation between serum IFN-γ concentrations, clinical type of psoriasis and severity of PV evaluated with the use of PASI score.

Influence of estrogen therapy on immune markers in postmenopausal women

Objective: To evaluate the impact of estrogen therapy on cellular and humoral immune markers in postmenopausal women.Methods: This prospective, controlled cohort study included 30 patients who used oral estradiol (1 mg) for 14–17 weeks and 28 patients who served as controls. Total leukocytes and leukocyte subtypes were counted and immunophenotyped by flow cytometry. The concentrations of immunoglobulins and pro- and anti-inflammatory cytokines were also measured in the peripheral blood before and after estrogen therapy. Immunoglobulin E level was measured by electrochemiluminescence, and levels of immunoglobulins A, G, and M were measured by nephelometry. Simultaneous quantification of multiple cytokines was performed by chemiluminescence to measure the serum concentrations of interferon gamma, interleukin (IL)-4, IL-6, IL-10, and IL-17.Results: Hematological cellular components were not significantly different before and after the use of estradiol (p = 0.332–0.984). Serum concentrations of immunoglobulins G, M, E, and A also remained stable (p = 0.248–0.845). Finally, cytokines were not modified throughout the 14–17 weeks of follow-up (p = 0.407–0.873).Conclusion: Isolated estrogen therapy with 1 mg of estradiol for 14–17 weeks in postmenopausal women did not modify any of the cellular or humoral immune markers analyzed in this study.

Interferon-gamma release assays and tuberculin skin testing for diagnosing latent Mycobacterium tuberculosis infection in at-risk groups in Poland

Objective/BackgroundThe diagnostics of latent tuberculosis infection in Poland using the tuberculin skin test is challenging due to the obligatory Bacillus Calmette–Guérin vaccinations. Interferon-gamma release assays are still very rarely used for diagnostics. We compared the tuberculin skin test and the QuantiFERON-TB Gold In-Tube test to evaluate the degree of latent tuberculosis infection in at-risk groups for tuberculosis (homeless, close contacts, periodic contacts, nursing-home attendees) and in healthy individuals. MethodsQuantiFERON-TB Gold In-Tube tests were carried out on 785 individuals from the homeless (n=150), close contacts (n=171), periodic contacts (n=163), nursing-home attendees (n=152), and healthy individuals (n=149). The tuberculin skin test was performed on 129, 156, 147, 148, and 121 participants, respectively. We evaluated the (a) correlation between serum concentrations of interferon gamma and the tuberculin-skin-test induration diameter; (b) between the number of QuantiFERON-TB Gold In-Tube-positive results and the tuberculin-skin-test diameter in the studied groups; and (c) agreement between both tests and the kappa coefficient using the tuberculin-skin-test diameters of 5, 10, and 15mm. ResultsLarger tuberculin-skin-test induration diameters were associated with elevated serum concentrations of interferon gamma. We found a positive correlation between the number of positive QuantiFERON-TB Gold In-Tube screening results and the tuberculin-skin-test induration diameter. The agreement between QuantiFERON-TB Gold In-Tube and tuberculin-skin-test screening results improved with increasing tuberculin-skin-test induration diameter. ConclusionBased on measures of tuberculin-skin-test induration diameter alone, it is difficult to diagnose latent tuberculosis infection with certainty. The agreement of the QuantiFERON-TB Gold In-Tube test increases with the tuberculin-skin-test diameter. Tuberculin-skin-test diameters larger than 15mm are more likely to be associated with active infection.

Increased ferroportin-1 expression and rapid splenic iron loss occur with anemia caused by Salmonella enterica Serovar Typhimurium infection in mice.

The Gram-negative intracellular bacterium Salmonella enterica serovar Typhimurium causes persistent systemic inflammatory disease in immunocompetent mice. Following oral inoculation with S. Typhimurium, mice develop a hematopathological syndrome akin to typhoid fever with splenomegaly, microcytic anemia, extramedullary erythropoiesis, and increased hemophagocytic macrophages in the bone marrow, liver, and spleen. Additionally, there is marked loss of iron from the spleen, an unanticipated result, given the iron sequestration reported in anemia of inflammatory disease. To establish why tissue iron does not accumulate, we evaluated multiple measures of pathology for 4 weeks following oral infection in mice. We demonstrate a quantitative decrease in splenic iron following infection despite increased numbers of splenic phagocytes. Infected mice have increased duodenal expression of the iron exporter ferroportin-1, consistent with increased uptake of dietary iron. Liver and splenic macrophages also express high levels of ferroportin-1. These observations indicate that splenic and hepatic macrophages export iron during S. Typhimurium infection, in contrast to macrophage iron sequestration observed in anemia of inflammatory disease. Tissue macrophage export of iron occurs concurrent with high serum concentrations of interferon gamma (IFN-γ) and interleukin 12 (IL-12). In individual mice, high concentrations of both proinflammatory (tumor necrosis factor alpha [TNF-α]) and anti-inflammatory (IL-10) cytokines in serum correlate with increased tissue bacterial loads throughout 4 weeks of infection. These in vivo observations are consistent with previous cell culture studies and suggest that the relocation of iron from tissue macrophages during infection may contribute to anemia and also to host survival of acute S. Typhimurium infection.

Umbilical Cord Serum Cytokine Levels and Risks of Small-for-Gestational-Age and Preterm Birth

While elevated levels of proinflammatory cytokines are clearly associated with preterm birth, the relation between cytokines and fetal growth is unclear. The authors examined associations between umbilical cord serum cytokine concentrations and risk of small-for-gestational-age (SGA) and preterm birth. This cross-sectional analysis was nested within a National Institute of Child Health and Human Development-University of Alabama population-based cohort study of high-risk prenatal care patients in Jefferson County, Alabama. Patients were enrolled between 1985 and 1988. For 370 singletons, umbilical cord serum concentrations of interferon gamma (IFN-gamma), tumor necrosis factor alpha, and interleukins 12p70, 4, and 10 were determined. Associations between each cytokine and SGA and preterm delivery were evaluated using log binomial regression. Increasing log concentration of tumor necrosis factor alpha was associated with an increased risk of preterm birth (risk ratio (RR) = 2.00, 95% confidence interval (CI): 1.31, 3.06). IFN-gamma was associated with a decreased risk of SGA birth (RR = 0.78, 95% CI: 0.61, 1.01). After stratification for preterm birth status, the association between IFN-gamma concentration and SGA birth was pronounced among preterm babies (RR = 0.56, 95% CI: 0.31, 1.01). The observations regarding IFN-gamma, which is involved in the activation of adaptive immune responses and regulation of trophoblast function, suggest that IFN-gamma levels at birth may be related to fetal growth restriction.

Circulating Levels of Interferon-γ in Course of Hepatitis C Virus-Related Arthritis

The aim was to weigh the serum concentrations of interferon gamma (IFN-gamma), a cytokine that enhances Th1-cell differentiation and suppresses collagen synthesis and angiogenesis, in two apparently distinct diseases, hepatitis C virus-related arthritis (HCVrA) and rheumatoid arthritis (RA), which share some overlapping immunological features. In this study, IFN-gamma serum levels were assayed by an ELISA method in 21 HCVrA patients and in 16 with RA. Very low IFN-gamma serum levels were found in five out of 21 patients with HCVrA and only in three out of 16 RA patients. Median value (range) resulted decrease in both HCVrA and RA groups, that is, 0.29 (0.04-1.49) versus 0.20 (0.05-1.18) IU/mL, P = 0.58. No correlation was evidenced with hepatic and arthritic involvements, nor between IFN-gamma serum levels and viral replication and moreover with the positivity of antinuclear antibody, rheumatoid factor, and anti-cyclic citrullinated peptides antibodies. These results show that IFN-gamma behavior appears similar in HCVrA and RA groups reinforcing the lack of significant differences between HCVrA and RA patients. Low circulating levels could be explained with the fact that IFN-gamma is not an isolate cytokine, but a piece of composite system regulated in a complex fashion, with many different factors contributing.

Mycobacteria-induced autoantibody production is associated with susceptibility to infection but not with host propensity to develop autoimmune disease.

Mycobacteria cause increase in autoantibody production in the host during the first weeks of infection. The level of the autoantibody enhancement varies widely in different hosts, suggesting that it depends on features of the host make-up. We have investigated the participation of two characteristics of the host in the modulation of mycobacteria-induced autoantibody production: (i) the host being genetically determined to later develop spontaneous autoimmune disease; (ii) the host being susceptible/resistant to mycobacterial infection. Mycobacterium avium infection was studied in 3-month-old mice that are prone (NZB and C57B1/6-lpr/lpr strains) or not (NZW and C.D2 strains) to develop, when older, autoimmune disease; these murine strains are either naturally susceptible (C57B1/6-lpr/lpr and NZW) or resistant (NZB and C.D2) to mycobacteria. Mycobacterium avium infection was produced by i.p. injection of 3 x 10(7) viable bacilli. At days 15 and 30 of the infection, we determined the following parameters: (i) number of cells producing natural autoantibodies (splenic cells showing surface antibodies against bromelain-treated mouse (BrM) erythrocytes); (ii) suppression of the primary response to T cell-dependent antigen (i.e. to sheep erythrocytes); (iii) immunoglobulin classes and IgG isotypes; (iv) titres of anti-dsDNA antibodies; and (v) serum concentrations of interferon-gamma (IFN-gamma). We found that the highest elevations in natural autoantibodies were associated with hosts being naturally susceptible to mycobacteria, but not with the host being genetically determined to later develop autoimmune disease. The rise in autoantibodies was predominantly of the IgM type, being associated with suppression of the T cell response and accompanied by increase in serum IFN-gamma. Mycobacteria failed to induce any significant enhancement in pathogenic anti-dsDNA antibodies. Our data suggest that the finding of a high level of autoantibodies during the early phase of mycobacterial infection reflects host susceptibility of the infectious agent, and that it is not related with its propensity to later develop autoimmune disorders.

Supplementing drinking water with Solutein did not mitigate acute morbidity effects of porcine reproductive and respiratory syndrome virus in nursery pigs

The objective of this study was to determine whether providing nursery pigs drinking water supplemented with spray-dried animal plasma (Solutein, American Protein Corporation Inc., Ankeny, IA) would reduce the detrimental impact of porcine reproductive and respiratory syndrome virus (PRRSV) infection. Sixty-four pigs were subjected to 1 of 4 treatment combinations (2 x 2 factorial arrangement) of Solutein [0 or 2.5% (wt/wt) in drinking water] and PRRSV (sterile medium or 5 mL of tissue culture infectious dose of high-virulence strain ATCC VR-2385). Pigs were provided the water treatments during a 1-wk period before inoculation as well as during a 2-wk period after inoculation. Growth performance was determined throughout the study, and several indicators of the immunological response to PRRSV and disease pathology were assessed in blood and tissue samples collected from pigs killed 7 or 14 d after inoculation. Before inoculation, pigs provided water supplemented with Solutein tended to eat less (P = 0.08) but tended to gain more BW (P = 0.13) than pigs provided tap water. Thus, Solutein markedly improved G:F (P < 0.01), after accounting for the DM provided by Solutein. Inoculation with PRRSV reduced ADG and ADFI (P < 0.01) irrespective of water treatment; however, the beneficial effects of Solutein on G:F persisted. Infection with PRRSV also reduced (P < 0.009) villus height and crypt depth in cranial, medial, and caudal segments of the small intestine and increased (P < 0.05) lung and spleen weight, the number of leukocytes in lung lavage fluid, and serum concentrations of interferon-gamma and IL-1beta regardless of water treatment. Collectively, these results indicate that supplementing water with spray-dried animal plasma improved feed efficiency but did not afford nursery pigs protection from the effects of PRRSV on growth and certain hematological traits.

Regulation of cysteine-rich intestinal protein, a zinc finger protein, by mediators of the immune response.

Cysteine-rich intestinal protein (CRIP), a member of the LIM protein family, has a unique double zinc finger motif as the defining feature. CRIP is highly expressed in intestine and immune cells. CRIP transgenic (Tg) mice and nontransgenic controls were challenged with lipopolysaccharide (LPS). Serum concentrations of interferon-gamma and tumor necrosis factor-alpha were less while those of interleukin-6 and -10 were greater in the Tg mice following LPS administration. CRIP-overexpressing splenocytes produce the same cytokine profile. These responses are consistent with a regulatory role for this protein in cell differentiation, which produces an imbalance in Th1 and Th2 cytokines. Stimulation of CRIP protein levels by LPS is eliminated in metallothionein knockout mice, suggesting metallothionein is the source of zinc for this zinc finger protein and, further, that this could reflect a relationship to the zinc nutritional status and to the aberrant Th1/Th2 cytokine balance observed in zinc deficiency.

Apoptosis and remodelling of beta cells by paracrine interferon-gamma without insulitis in transgenic mice.

To examine whether interferon-gamma destroys islet beta cells directly or indirectly through lymphocyte activation, or whether direct action of interferon-gamma on beta cells by itself induces diabetes without insulitis. To avoid possible nonspecific breakdown of beta cells by transgenic overexpression of interferon-gamma by the insulin promoter, we generated transgenic mice expressing interferon-gamma under the control of rat glucagon promoter (RGP-IFN-gamma-Tg mice). The absence of insulitis in RGP-IFN-gamma-Tg mice enabled us to investigate the direct effects of paracrine interferon-gamma. In RGP-IFN-gamma-Tg mice, serum concentrations of interferon-gamma and tumour necrosis factor-alpha (TNF-alpha) were 50 and 6 times higher than those in their littermates, respectively, and glucose-responsive insulin secretion decreased to one-half the level of that in the littermates. Transgenic interferon-gamma induced remodelling of beta cells where apoptosis of many beta cells was compensated by their vigorous regeneration and diabetes did not occur in most of the RGP-IFN-gamma-Tg mice. Interferon-gamma alone is insufficient for the complete destruction of beta cells in vivo, and factors other than interferon-gamma including activated lymphocytes or other cytokines, are necessary in addition to interferon-gamma for the development of Type I (insulin-dependent) diabetes mellitus.

Lipopolysaccharide decreases scavenger receptor mRNA in vivo.

Lipopolysaccharide (LPS) downregulates scavenger receptor (ScR) activity in cultured macrophages through release of tumor necrosis factor-alpha (TNF-alpha). However, LPS administration in vivo stimulates cytokine release from both macrophages and lymphocytes, the combined effects of which could alter ScR expression differently from TNF-alpha in isolation. To investigate whether LPS regulates ScR in vivo, 10 microg/g was injected i.p. into Swiss Webster mice. Administration of LPS produced a profound decrease in hepatic ScR mRNA, with reductions of 74% +/- 8% at 2 h that returned to baseline levels by 6 h. Changes in ScR mRNA abundance coincided with changes in serum concentrations of TNF-alpha, which peaked at 2 h (1320 +/- 309 pg/ml) and returned to preinjection concentrations at 4 h. Serum concentrations of interferon-gamma (IFN-gamma) did not increase until 4 h after injection of LPS. There was no effect on ScR mRNA abundance following LPS administration to LPS-resistant strains of mice, C3H/HeJ and IFN-gamma receptor-/-. The LPS-induced reduction in ScR mRNA in Swiss Webster mice was not sufficiently sustained to affect receptor function, as determined by the kinetics of [(125)I]-acetylated LDL clearance from plasma. Therefore, as observed in cultured cells, LPS administration to mice decreases ScR mRNA despite the release of several cytokines in vivo.

Serumkonzentrationen von Interferon γ, Interleukin-6 und Neopterin bei Patienten mit infektiöser Mononukleose und anderen Epstein-Barr Virus-assoziierten lymphoproliferativen Erkrankungen

Serum levels of interferon gamma, interleukin-6 and neopterin were determined in 15 patients with different forms of Epstein-Barr virus-associated diseases: acute self-limiting infectious mononucleosis, chronic active infectious mononucleosis and X-linked lymphoproliferative syndrome. In patients with acute type of infection, neopterin, interferon gamma and interleukin-6 were elevated in nearly all patients. In contrast, the situation was less clear-cut in the other EBV-associated diseases; particularly interleukin-6 was undetectable in most cases. The results suggest that concomitant measurement of these diverse immune activation markers may provide interesting insights into the interactions between the virus and the host, and may also lead to therapeutic consequences.

CD4 T-Lymphocyte Activation in Acute Severe Asthma: Relationship to Disease Severity and Atopic Status

Lymphocytes are prominent among the inflammatory cells infiltrating the asthmatic airways, and several studies have suggested that cell-mediated immunity may play a role in the pathogenesis of chronic asthma. We have measured (1) the expression of activation markers on the CD4+ and CD8+ T-lymphocyte phenotypic subsets in the peripheral blood of patients hospitalized with acute severe asthma ("status asthmaticus"), and (2) the serum concentrations of two proteins elaborated by activated T-lymphocytes (interferon-gamma and the soluble interleukin-2 receptor). The results were compared with those in control subjects (mild asthma, chronic obstructive airway disease, and normal). CD4+ lymphocytes from patients with acute severe asthma showed significant increases in the expression of three surface proteins associated with lymphocyte activation (interleukin-2 receptor [IL-2R], class II histocompatibility antigen [HLA-DR], and "very late activation" antigen [VLA-1]) as compared with those from normal control subjects. In contrast, CD8 cells were devoid of IL-2R and VLA-1, in both patients with acute severe asthma and control subjects, and the expression of HLA-DR on these cells was not increased above that of control subjects. The serum concentrations of interferon-gamma and soluble IL-2R were significantly elevated in patients with acute severe asthma as compared with all the control groups. Concentrations decreased as the patients improved clinically during the first 3-day period of hospital treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of Serum Interferon Gamma and Neopterin Concentrations in Africans with Various Diseases

Summary Concentrations of interferon gamma in serum and of neopterin in serum and urine were determined in 55 Tanzanians attending a local hospital for various diseases or complaints. For comparison, serum concentrations of interferon gamma and of neopterin were also measured in 76 clinically healthy Austrian blood donors. Both interferon gamma and neopterin concentrations were significantly higher in patients than in blood donors. Both analytes were significantly correlated with each other, and both exhibited similar behaviour in dependence on clinical diagnosis. The results support use of neopterin determination for indirect measurement of endogenous production of interferon gamma.