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Biomedical subjects

I Rosztóczy

Publications and source records attributed to I Rosztóczy.

At least 19 recordsLinked to original sources

Different staphylococcal strains elicit different levels of production of T-helper 1-inducing cytokines.

Cytokine production has been implicated in the pathogenic mechanisms of infections caused by the staphylococci, since these bacteria may act as strong cytokine inducers. To gain deeper insight into the Th1 immune response activated by these bacteria, we have analyzed the interferon (IFN), interleukin-12 (IL-12) and IL-18-inducing activities of different Staphylococcus aureus (S. aureus), S. epidermidis and S. saprophyticus strains in human monocytes and murine bone marrow macrophages. A large majority of the S. aureus strains elicited the simultaneous production of IL-12 p70 and IFN-alpha in the human monocytes, while the S. epidermidis and S. saprophyticus strains induced only a low level of production, if any, of these cytokines. Furthermore, a majority of the S. aureus strains induced significantly higher IL-12 p70 and IL-18 titers in the murine bone marrow macrophages than did the S. epidermidis and S. saprophyticus strains. As IL-12, IL-18 and IFN-alpha stimulate Th1 differentiation synergistically, we suggest that S. aureus strains bias the immune response toward a Th1 phenotype, whereas S. epidermidis and S. saprophyticus strains provide a weaker stimulus for the production of Th1-inducing cytokines, and accordingly possibly elicit a less extensive Th1-associated adaptive immunity.

Animals↗

Interleukin 6 levels in synovial fluids of patients with different arthritides: correlation with local IgM rheumatoid factor and systemic acute phase protein production.

Interleukin 6 (IL-6), a multifunctional cytokine particularly active in regulation of the acute phase response, governs the terminal maturation of B lymphocytes and participates in early activation of T cells. IL-6 levels of synovial fluids of 153 patients with different arthritides were measured by a simple sandwich enzyme immunoassay. Highest IL-6 concentrations were detected in patients with rheumatoid arthritis (RA), particularly in those characterized by very active general symptoms and severe joint pain. High IL-6 levels were detected in patients with juvenile RA with polyarticular onset of disease and in gout. Corresponding to the suggested in vivo relevance of IL-6, dose correlation of IL-6 levels with the synovial IgM rheumatoid factor accumulation was demonstrated. The rate of the correlation between synovial IL-6 level and concentration of serum C-reactive protein in RA was inversely proportional to the dose of steroid treatment in patients with RA.

Arthritis↗

Lack of correlation in the interferon-induced small Mw 2-5A synthetase mRNA levels and sensitivity of two L cell sublines to the antiviral and priming effects of interferon.

MuIFN-alpha/beta at a concentration of 0.5 IU/ml exerted both antiviral and priming effects in the B, but not in the M subline of L929 cells. This concentration of IFN did not affect the small size 2-5A synthetase mRNA levels in either sublines, as determined by a Northern blot technique. Pretreatment with 5 or 50 IU/ml IFN resulted in more pronounced antiviral and priming effects in the L929B than in the L929M cells. However, the enhancements of the 2-5A synthetase mRNA levels due to the pretreating IFN dose were similar in both sublines.

Animals↗

Association between chemiluminescence stimulating and IL-2 inducing activities of Staphylococcus aureus strains in human and mouse mononuclear cells.

The plastic adherent fraction of human mononuclear cells (MNC) responded with maximal chemiluminescence (CL) upon stimulation with greater than or equal to 1000 bacteria per cell of heat killed preparations of Staphylococcus aureus strains. Different strains had different CL stimulating activities and their sequences were similar on MNC from different blood donors. IL-2 inducing and CL stimulating activities seem to be parallel features of S. aureus strains, since their sequence set ups established on the basis of these two properties were almost identical. The same phenomenon could also be observed in a mouse system, in which activated peritoneal cells (PC) were the most active CL exhibiting population. The IL-2 inducing activity of staphylococci in mouse spleen cells and their CL stimulating activity in activated PC followed a similar pattern too. The sequences of CL inducing activities of different staphylococcal strains were in good agreement in human and mouse cells. Representative strains with high, moderate and low CL inducing activities followed the same sequence of virulence for mice.

Animals↗

The role of the various human peripheral blood mononuclear cells in the production of Sendai virus-induced interferon: IFN mRNA studies.

We have studied the relative contribution made to the production of interferon (IFN) in vitro in response to Sendai virus by the cells of different types present in human peripheral blood, with particular emphasis on the amounts of poly(A) plus RNA extractable from each subpopulation and its content of IFN mRNA. Peripheral blood cells were fractionated by conventional techniques, and the amounts of IFN made after induction with Sendai virus were measured. The proportion of IFN-producing cells in the various fractions was determined by immunofluorescent staining. Poly(A) plus RNA was extracted from each population and the content of IFN mRNA determined by microinjection into Xenopus laevis oocytes. Information obtained in these three ways was essentially concordant, and showed that monocytes and E rosette-negative lymphocytes predominantly contribute to IFN production.

Animals↗

Interferon production by normal mouse tissues in organ cultures.

Freshly removed tissues of normal untreated mice produced relatively high amounts of interferon (IFN) in organ cultures. Lymph nodes, subcutaneous tissue, and the capsule of the kidney were the most active IFN producers. The abdominal wall and the thigh muscle were less active, whereas the lungs and spleen, similarly to the peritoneal exudate and bone marrow cells, produced only threshold amounts of IFN. Liver cultures did not produce IFN under these experimental conditions. Cultures prepared from IFN-pretreated animals produced three- to fourfold more IFN. Homogenates of tissue prepared immediately after their removal did not contain a detectable amount of IFN. The bulk of the IFN activity was produced during the first 6 h of incubation at 37 degrees C. Omission of serum from the culture medium, and the presence of 50 micrograms/ml of polymyxin B, did not inhibit IFN production. Cultures incubated at 0 degrees did not release any IFN. The IFN activity produced by all types of tissue was pH 2 resistant and it was neutralized by an antiserum to murine (Mu) IFN-beta. Different strains of mice produced comparable amounts of IFN under the present experimental conditions.

Animals↗

Effects of phorbol myristate acetate on interleukin-2 and accompanying interferon production of human leukocytes induced by heat-inactivated Staphylococcus aureus.

Interleukin-2 (IL-2) production induced by heat--inactivated Staphylococcus aureus (SAU) was enhanced by simultaneous addition of phorbol myristate acetate (PMA). The effect was optimal at a concentration of 10 ng/ml SAU; in the presence of 10 ng/ml PMA, the amount of SAU required for maximal IL-2 production was lower. The kinetics of SAU and of SAU plus PMA-induced IL-2 production were similar. Stimulated mononuclear cells produced interferon (IFN) in addition to IL-2. The titre of accompanying IFN was decreased in cultures stimulated with the SAU plus PMA combination. Plastic nonadherent sheep erythrocyte-positive cells were the most active in the SAU-induced IL-2 production. In contrast, the bulk of the IFN activity was produced by the nonadherent E rosette-nonforming cells. Neutralization of IFN with specific antibodies and pH 2 treatment indicated that SAU-induced IFN consisted mainly of alpha-IFN.

Hot Temperature↗

Priming of Staphylococcus aureus-induced interferon production in human buffy coat leukocytes by human interferon-alpha pretreatment.

Human buffy coat leukocytes produced interferon (IFN) in response to induction with heat-killed Staphylococcus aureus. Pretreatment of cell with 150 IU/ml human interferon-alpha (HuIFN-alpha) for 3 h enhanced the IFN production by about four- to eight-fold. The simultaneous presence of HuIFN-alpha and gamma in the culture supernatants was indicated by parallel titrations on human embryo fibroblasts (HEF) and MadinDarby bovine kidney (MDBK) cells and also by the distribution of the peak IFN activities after Sephacryl S-200 gel filtration.

Humans↗

Staphylococcus aureus and Staphylococcus epidermidis strains differ in interleukin 2 inducing activity.

Heat-killed preparations of different Staphylococcus aureus and Staphylococcus epidermidis strains were compared for interleukin 2 (IL-2) inducing activity in cultures of human mononuclear cells (MNC). S. aureus strains exhibited a strong individual variation, but they induced considerably more IL-2 than did S. epidermidis strains. Enterotoxin production, coagulase production, pigment formation and the phage type of the staphylococci showed no strict correlation of any of these properties with the IL-2 inducer activity. The results indicate that the IL-2 inducing activity may be a differential feature of S. aureus and S. epidermidis.

Cells, Cultured↗

Different interferon-producing capacities of L929 cell sublines and the enhancement of interferon production by priming are controlled pretranslationally.

Two sublines of mouse L929 cells designated L929B and L929M were studied. The L929B cells, which displayed a 2-3-fold higher IFN production in response to Sendai virus than that of the L929M cells, had a higher sensitivity to the antiviral and priming effects of IFN and were more resistant to VSV. In good accord with the amount of IFN produced, more translatable IFN mRNA was isolated from the L929B cells. IFN production and IFN mRNA activities were proportionally increased in the IFN-primed cultures of both sublines. Results indicate that both inherent and priming-induced increased-IFN production are based on pretranslational control mechanisms.

Animals↗

Effects of interferons-alpha, -beta, and -gamma on human interleukin-2 production.

Interleukin-2 (IL-2) production was stimulated with staphylococcus enterotoxin A, heat-killed Staphylococcus aureus, or concanavalin A (ConA) in cultures of human peripheral blood mononuclear cells (PBMC). IL-2 was characterized by its effect on IL-2-dependent cytotoxic T lymphocytes (CTLL cells) and mouse thymocytes. Pretreatment of PBMC with greater than or equal to 100 IU/ml of human-alpha (HuIFN-alpha) or interferon-beta (HuIFN-beta), or with greater than or equal to 10 IU/ml HuIFN-gamma for 4 h enhanced the IL-2 production. The effects of 20-h IFN treatments were less pronounced or they exerted an inhibitory effect. Our results indicate that IFNs modulate IL-2 production, which in turn can mediate some of the immunomodulatory effects of IFNs.

Concanavalin A↗

Study of the in vivo priming effect of interferon in mice.

Intramuscular injection of mice with 2000 IU/g partially purified murine interferon (IFN) alpha/beta 3 h before the induction of IFN by intraperitoneally administered 3 micrograms/g poly rI:rC enhanced early IFN production. The differences between the serum IFN levels of IFN-pretreated and control animals were about 10-fold during the first 2 to 3 h of in vivo IFN production. In later stages these differences tended to decrease, and from 8 h post-induction they disappeared. IFN exerted its in vivo priming activity equally after intravenous, intraperitoneal or intramuscular injection. A similar enhancement of IFN production was observed when it was induced by poly rI:rC administered either intraperitoneally or intramuscularly. The duration of IFN pretreatment influenced the establishment of the in vivo primed state. Following administration of 2000 IU/g murine IFN alpha/beta intramuscularly, maximal priming developed after 3 h, and no primed IFN response was detected when the inoculation of IFN preceded inducer administration by 12 h or more. The manifestation of in vivo priming was optimal when 1500 to 3000 IU/g pretreating doses of IFN were applied. Reduction of the amount of injected IFN below this level markedly decreased priming, indicating a time- and dose-dependent induction of priming in vivo.

Animals↗

Combined effects of amantadine and interferon on influenza virus replication in chicken and human embryo trachea organ culture.

Amantadine (greater than or equal to 100 micrograms/ml) treatment of chicken or human trachea organ cultures 6 h before infection inhibited influenza virus replication. Chicken or human leukocyte IFN evoked antiviral resistance in the cells of the homologous organ cultures only at a concentration of 100 U/ml or more. Treatment of organ cultures with combinations of the two substances resulted in an additive effect on influenza virus replication in both chicken and human tissues.

Amantadine↗

Priming of interferon production in human embryo fibroblasts by alpha, beta and gamma interferons.

Pretreatment of human embryo fibroblasts with homologous alpha, beta and gamma interferons (IFNs) exerted a priming effect on both the ordinarily poly I: C-induced and the superrinduced human IFN beta production. The priming activities of HuIFN-alpha and beta were equivalent while HuIFN-gamma proved to be somewhat inferior in this respect. DEAE-dextran enhanced the efficacy of induction when it was used in combination only with poly I:C. No such effect could be observed in the superinduced cultures. A correlation was found between the amount of IFN produced by the primed or superinduced human embryo fibroblasts and the quantity of extractable polyadenylated translatable IFN mRNA in these cells.

Cells, Cultured↗

Modulation of lymphokine production by interferon.

Pretreatments with relatively low (25-250 U/ml) concentrations of interferon (IFN) enhanced while 5000-10 000 U/ml concentrations of IFN inhibited leukocyte inhibitory factor (LIF) and migration inhibitory factor (MIF) production of concanavalin A (Con A) stimulated human leukocytes. The lymphokine regulatory activity of IFN correlated with the antiviral activity of IFN preparations regardless of their specific activity and it showed species specificity. Modulation of lymphokine production depended not only upon the amount of IFN used but also on the length of IFN pretreatment. Blocking of lymphokine production by high concentration of IFN could not be explained by the effect of IFN on cell viability.

Cell Survival↗