Treatment of adjuvant arthritis in mice with yeast superoxide dismutase.

Yeast Cu/Zn superoxide dismutase (SODy) was used for treatment of adjuvant-induced arthritis in mice. SODy was applied intraperitoneally (i.p.) in doses of 10 mg/kg (30,000 U/kg) and 30 mg/kg (90,000 U/kg) one or three times daily on consecutive days. It was very effective in reducing the paw swelling whether administered before or immediately after induction or when the treatment began at the onset of inflammation or at the peak of the arthritic process. The effect of yeast SOD was compared to that of commercial SOD from bovine erythrocytes (SODb), as well as with indomethacin treatment. Histological data confirmed the antiinflammatory effect of yeast SOD. The schedules and doses tested did not elicit anti-SOD antibodies in serum.

Effect of Escherichia coli L-form cytoplasmic membranes on the interaction between macrophages and Lewis lung carcinoma cells: scanning electron microscopy.

Scanning electron microscopy (SEM) investigations on the interactions between peritoneal macrophages from Lewis lung carcinoma (LLC)-bearing mice and LLC tumour cells during 21 days after tumour implantation were carried out. The action of lipopolysaccharide (LPS)-containing cytoplasmic membranes (CM), from the stable protoplast type L-form of Escherichia coli, on the activity of in vitro phagocytosis was studied; CM induced a continuous increase in macrophage numbers. Activation of macrophage surfaces in healthy and tumour-bearing mice was established. Lamelipods, pseudopods and migration fringes 14 days after CM application were seen. Crater-like cavities deeply in the macrophage cells as well as adherent or prominent engulfed tumour cells within macrophages were observed during in vitro interaction with LLC cells. Macrophages from tumour-bearing mice without CM treatment showed less activation evaluated by SEM during earlier stages of tumour growth. The SEM investigation proved the temporary stimulating effect of E. coli L-form CM on the cell surface activation of peritoneal macrophages in healthy and LLC-bearing mice.

Designing an artificial ecological mesocosm for the study of Cd and Pb impact on the immune system of experimental animals.

Studies on the influence of high heavy metal concentrations (Pb and Cd) on the immune status of experimental animals were carried out. The experiments were performed with Balb/c mice and Pb and Cd concentrations 30- and 50-fold above the limit admissible concentrations (LAC), respectively. A slight increase in the phagocytic activity after 5 days of treatment with high doses of the heavy metals (HM) and its significant activation on the 30th day for both concentrations were observed. Low doses of the HM cause significant increase in the spontaneous production of H2O2 on the 30th day of the experiment. The production of H2O2 by stimulation with PMA macrophages was also activated on the 30th day but to a lower degree and only with the high doses of the HM. Inhibition of the alternative pathway of complement activation was observed in animals treated with low and high doses of the HM for 90 days.

Effect of a total extract from Fraxinus ornus stem bark and esculin on zymosan- and carrageenan-induced paw oedema in mice.

This study investigates the total ethanol extract (TE) of the stem bark of Fraxinus ornus and its constituent esculin (EN). They inhibited classical pathway (CP) and alternative pathway (AP) of complement activation in mouse serum. After intraperitoneal administration the total extract displayed antiinflammatory activity in both zymosan- and carrageenan-induced paw oedema in mice. The results suggest that the traditional use of Fraxinus ornus stem bark extracts in the treatment of inflammatory disorders is at least partially due to its coumarin constituents.

Antiinflammatory effect of superoxide dismutase (SOD). Comparison between yeast and bovine SOD on some complement-mediated reactions in vitro and in vivo.

The effect of CulZn superoxide dismutases from yeast cells (SODy) and commercial SOD from bovine erythrocytes (SODb) on zymosan-induced inflammation in mice and on complement activity in normal human serum (NHS) was studied. Zymosan-induced oedema formation was moderately suppressed by SODb. The alternative pathway (AP) activity in mouse serum was strongly inhibited after i.p. treatment with SODy. Comparison between the two enzymes showed different mode of action on the classical pathway (CP) as compared to the AP of complement activation. The inhibitory effect caused by SODy was more pronounced and strongly time- and temperature-dependent. SODy affected several activation steps in the complement cascade, while the inhibition caused by SODb was mainly directed to C1 of the complement activity. The powerful action of SODy on AP activity may be attributed to the oligosaccharide moiety in the enzyme molecule from yeast origin.

Immunomodulating activity of ginsenoside Rg1 from Panax ginseng.

The immunomodulatory activity of ginsenoside Rg1 from Panax ginseng was studied in mice using sheep red cells as the antigen. It was found that ginsenoside Rg1 at a dose of 10 mg/kg administered for three consecutive days before immunization increased the number of spleen plaque-forming cell, the titers of sera hemagglutinins as well as the number of antigen-reactive T-cells. Ginsenoside Rg1 also increased the number of T-helper cells with respect to the whole T-cell number and the splenocyte natural killer activity. Ginsenoside Rg1 induced an augmentation of the production of IL-1 by macrophages and exerted a direct mitogenic effect on microcultured thymus cells. Ginsenoside Rg1 also partly restored the impaired immune reactivity by cyclophosphamide treatment.

Modulation of the human immune response by the non-toxic and non-pyrogenic adjuvant aluminium hydroxide: effect on antigen uptake and antigen presentation.

The regulatory effects of an adjuvant (aluminium hydroxide) on the early phase of the immune response have been investigated. Adsorbing a soluble antigen (tetanus toxoid) to aluminium hydroxide led to a significant increase (P less than 0.001) in antigen-induced T-cell proliferation (macrophage-T-cell interaction, MTI) making aluminium hydroxide-adsorbed antigens especially suitable to study immunoregulatory changes in the early phase of the immune response. First studies revealed that this increase was due to an enhancement of antigen uptake by the antigen-presenting cell. However, under conditions allowing for the uptake of comparable amounts of soluble (TTs) or aluminium hydroxide-absorbed (TTAL) antigen, T-cell proliferation in response to TTAL was still higher than in response to TTS. This difference was especially pronounced if suboptimal antigen concentrations were used and could be explained by differences in the TTS-versus TTAL-induced release of interleukin-1 (IL-1). Pulsing with TTAL led to a substantial increase in IL-1 release by monocytes (MO) which then subsequently augmented antigen-induced T-cell proliferation. This was further supported by addition of exogenous IL-1 to cultures of T cells and TTS-pulsed MOs, which also significantly increased the T cells' proliferative response. These findings demonstrate that in the early phase of the immune response, aluminium hydroxide exerts its regulatory effect at the level of the antigen-presenting and mediator-releasing accessory cell.

Effect of experimentally induced trichinellosis on the infection with Erysipelothrix rhusiopathiae in rats.

Infection with Erysipelothrix rhusiopathiae in rats infested 20 days earlier with Trichinella spiralis developed more slowly, the clinical and pathoanatomic changes in the joints were expressed to a less extend, and the mortality rate was lower. The erythrocyte sedimentation rate, the precipitin formation and the phagocytic activity of the macrophages did not considerably change. Experiments carried out to elucidate this fact did not reveal any antigenic or antagonistic relationships between parasite and bacterium nor any protective effect of the host's serum. The inhibitory influence of corticosteroids on the defence forces was not completely manifested in the rats infested. This fact might be explained by interrelations depending both on the cycle of helminth development and on the non-specific immunological reactivity of the organism, the latter being stimulated by the helminth invasion.