Effects of Secondary Metabolites of Permafrost Bacillus sp. on Cytokine Synthesis by Human Peripheral Blood Mononuclear Cells.

We studied the effects of secondary metabolites of Bacillus sp. isolated from late Neogene permafrost on secretion of proinflammatory (TNF-α, IL-1ß, IL-8, IL-2, and IFNγ) and antiinflammatory (IL-4 and IL-10) cytokines by human peripheral blood mononuclear cells. It was found that metabolites of Bacillus sp. produced more potent effect on cytokine secretion than mitogen phytohemagglutinin and metabolites of Bacillus cereus, medicinal strain IP5832. Activity of metabolites depended on the temperature of bacteria incubation. "Cold" metabolites of Bacillus sp. (isolated at -5°C) primarily induced Th1-mediated secretion of IFNγ, while "warm" metabolites (obtained at 37°C) induced Th2-mediated secretion of IL-4. The results suggest that Bacillus sp. metabolites are promising material for the development of immunomodulating drugs.

Reparation and Immunomodulating Properties of Bacillus sp. Metabolites from Permafrost.

An ointment containing metabolites of Bacillus sp. microorganisms isolated from permafrost samples was applied onto the skin wound of BALB/c mice. Metabolites isolated during culturing of Bacillus sp. at 37°C produced a potent therapeutic effect and promoted wound epithelialization by 30% in comparison with the control (ointment base) and by 20% in comparison with Solcoseryl. Treatment with Bacillus sp. metabolites stimulated predominantly humoral immunity, reduced the time of wound contraction and the volume of scar tissue, and promoted complete hair recovery. These metabolites can be considered as modulators of the wound process with predominance of regeneration mechanisms.

Experimental study of the effects of permafrost microorganisms on the morphofunctional activity of the immune system.

The immunobiological potential of a new microorganism species isolated from permafrost specimens (PMO strain 3M) collected from the Mammoth Mountain in Yakutia was studied in laboratory mice. PMO injected intraperitoneally in doses of 2500 to 50 × 10(6) microbial bodies caused characteristic dose-dependent effects on the structure and functions of the immune system (thymus and spleen indexes, functional activity of splenic macrophages, cellular and humoral immunity). Doses of PMO stimulating functional activities of both cellular and humoral immunity were detected.

Effects of short-term hypothermal and contrast exposure on immunophysiological parameters of laboratory animals.

Experiments on inbred animals showed that short-term exposure in cold water significantly modified structural and functional parameters of the immune system at different levels of its organization, from bone marrow hemopoiesis to effector stage of the immune response to antigen. The thermal factor caused changes in nonspecific and specific mechanisms of the immune system. Hypothermal exposure (7-9 degrees C, 5 sec) increased the thymic index and bone marrow lymphocyte count, reduced absorption capacity and stimulated metabolic activity of phagocytes, stimulated cell-mediated and suppressed humoral immunity. Contrast exposure in cold and hot water (7-9 degrees C, 5 sec/40-42 degrees C, 30 sec) increased monocyte count in bone marrow and reduced it in the their peripheral blood, reduced metabolic activity of phagocytes, stimulated cell-mediated and suppressed humoral immunity. These data demonstrate physiological mechanisms of interactions between the thermoregulatory and immune systems.

[Influence of permafrost microorganisms on the quality and duration of life of laboratory animals].

Microorganisms of genus Bacillus strain 3M (permafrost microorganisms--PM), allocated from the samples of permafrost soils from Mamontova Mountain (Yakutia) are influenced by the quality and duration of life of elderly mice. PMs were injected intraperitoneally to CBA mice at the age of 17 months. Motion activity, muscular force (lifting of cargo test), food instinct activity (dosed starvation test) and cellular immunity activity (reaction of delayed-type hypersensitivity in vivo) of animals have increased, and psychoemotional condition of animals has improved under influence of PM. Average duration of life has increased by 9.19%, minimal duration of life--by 41.93%, maximal duration of life--by 7.68%. Duration of survival (the remaining life after injection of microorganisms) has increased more significantly: minimal--by 141.9%, on the average--by 28.0%, maximal--by 20.4%. Mechanisms of PM influence on increase of laboratory mice duration of life up to the top specific limit through the positive influence on quality of their life are discussed.