E. G. Novoselova

Microwaves and cellular immunity: I. Effect of whole body microwave irradiation on tumor necrosis factor production in mouse cells

Whole body microwave sinusoidal irradiation of male NMRI mice with 8.15-18 GHz (1 Hz within) at a power density of 1 microW/cm2 caused a significant enhancement of TNF production in peritoneal macrophages and splenic T lymphocytes. Microwave radiation affected T cells, facilitating their capacity to proliferate in response to mitogenic stimulation. The exposure duration necessary for the stimulation of cellular immunity ranged from 5 h to 3 days. Chronic irradiation of mice for 7 days produced the decreasing of TNF production in peritoneal macrophages. The exposure of mice for 24 h increased the TNF production and immune proliferative response, and these stimulatory effects persisted over 3 days after the termination of exposure. Microwave treatment increased the endogenously produced TNF more effectively than did lipopolysaccharide, one of the most potential stimuli of synthesis of this cytokine. The role of microwaves as a factor interfering with the process of cell immunity is discussed.

Effects of low‐power laser radiation on mice immunity

Background/purpose: Because of large interest in biological effects of laser radiation used in laser therapy, the effect of extremely low‐level red laser light intensity on the immune cell activity has been studied in the animal model with well‐characterized macrophage and T cell populations as responder cells producing cytokines, protective proteins, active oxygen, and nitric compounds. To study of the possible side effects of laser immunotherapy we monitored the productions of cytokines, nitric oxide (NO), and heat shock protein 70 (Hsp70) in mice subjected to a periodic laser exposure for 1 month.

Naturally occurring antioxidant nutrients reduce inflammatory response in mice.

The effects of mixed dietary coenzyme Q(9), alpha-tocopherol, and beta-carotene on immune cell activity and blood cytokine profile were studied in peritoneal macrophages, spleen lymphocytes, and blood plasma from mice with acute inflammation induced by lipopolysaccharide (LPS). The activity of each fat-soluble antioxidant was also investigated separately in several model systems, both in vivo and in vitro. NMRI male mice were fed a diet supplemented with fat-soluble antioxidants for 15 days prior to LPS injection. LPS-induced inflammation resulted in induction of cellular production of pro-inflammatory cytokines such as TNF-alpha, IL-1alpha, IL-1beta, IL-2, IL-6, IFN-gamma, and also IL-10, an anti-inflammatory cytokine, and subsequent accumulation of these cytokines in blood plasma. In animals fed the antioxidant-rich diet, the inflammatory response to LPS injection was significantly reduced. The production of anti-inflammatory cytokine IL-10 in response to toxic stress and its accumulation in plasma were not modified by the diet. In addition, the expression of the inducible form of heat-shock protein 70 in mice treated with endotoxin was reduced in the animals pretreated with the antioxidant-rich diet. We showed that the diet suppressed phosphorylation of NF-kappaB, I kappaB kinase and SAPK/JNK proteins, thereby preventing the activation of the NF-kappaB kinase and SAPK/JNK signaling pathways in LPS-treated mice. In this report we demonstrate the potential effectiveness of naturally occurring antioxidant nutrients in the reduction of the inflammatory response. Therefore, it may be possible to develop novel therapeutic combinations, containing coenzyme Q(9), alpha-tocopherol, and beta-carotene, which promote immune stimulation.

MICROWAVES AND CELLULAR IMMUNITY. II. IMMUNOSTIMULATING EFFECTS OF MICROWAVES AND NATURALLY OCCURRING ANTIOXIDANT NUTRIENTS

The effect of 8.15-18 GHz (1 Hz within) microwave radiation at a power density of 1 microW/cm2 on the tumor necrosis factor (TNF) production and immune response was tested. A single 5 h whole-body exposure induced a significant increase in TNF production in peritoneal macrophages and splenic T cells. The mitogenic response in T lymphocytes increased after microwave exposure. The activation of cellular immunity was observed within 3 days after exposure. The diet containing lipid-soluble nutrients (beta-carotene, alpha-tocopherol and ubiquinone Q9) increased the activity of macrophages and T cells from irradiated mice. These results demonstrate that irradiation with low-power density microwaves stimulates the immune potential of macrophages and T cells, and the antioxidant treatment enhances the effect of microwaves, in particular at later terms, when the effect of irradiation is reduced.

Thymulin, a thymic peptide, prevents the overproduction of pro-inflammatory cytokines and heat shock protein Hsp70 in inflammation-bearing mice.

The effects of synthetic analogue of peptide hormone thymulin, which is normally produced by thymic epithelial cells, on immune cells activity and blood cytokine profile had been studied in male NMRI mice with acute inflammation induced by injection of lipopolysaccharide from gram-negative bacteria (LPS, 250 μg/100 g of body weight). Inflammation induced by LPS resulted in accumulation of several plasma pro-inflammatory cytokines, IL-1β, IL-2, IL-6, TNF-α, interferon-γ, and also IL-10, anti-inflammatory cytokine. Thymulin previously injected in dose of 15 μg/100 g body weight, prevented the accumulation of proinflammatory cytokines in plasma. Thymulin also prevented LPS-induced up-regulation of production of several cytokines by spleen lymphocytes and peritoneal macrophages. Added in vitro, thymulin decreased the peak of TNF-α production in macrophages cultivated with LPS. In addition, thymulin lowered the peak of Hsp70 production induced by LPS treatment. The results indicate that thymulin having significant anti-inflammatory effect may be promising in clinical application.

Thymus hormones as prospective anti-inflammatory agents

Importance of the field: Inflammatory diseases are characterized by severe immune imbalances, leading to excessive or inappropriate release of mediators, which, in turn, result in massive damage to organs and systems. Effective means to control inappropriate immune reactions are often life-critical needs. Available data on the role of thymus-derived hormones in inflammation show their great potential. Areas covered in this review: The review aims to systematize information for the last two decades on immune system regulation by thymic peptide hormones, with a primary focus on the role of these hormones in the systemic inflammatory response and inflammatory diseases. Anti-inflammatory potential of three thymic hormones – thymulin, thymosin-alpha, and thymopoietin – is discussed, reviewing recently published clinical and experimental studies. What the reader will gain: Our analysis revealed the regulation of inflammatory processes via thymic hormones that could be prospective for therapeutic application. This regulation may be mediated through thymic hormone effects on peripheral immune cell activities and bidirectional coupling between thymic hormones and the hypothalamic–pituitary–adrenal axis. Take-home message: In view of the role of thymic hormones in immune and neuroendocrine systems, they could be suitable as therapeutic agents for inflammation.

Production of tumor necrosis factor in cells of hibernating ground squirrels Citellus Undulatus during annual cycle

TNF production has been studied in peritoneal macrophages and splenic T cells of Arctic Yakutian ground squirrel (Citellus Undulatus Pallas) in hibernating and awake animals in winter and in prehibernating autumn as well as in active euthermic spring-summer animals. A high level of TNF production in macrophages of ground squirrel is observed over the active period and during arousals in winter. There are no significant season variations in TNF production in splenic T lymphocytes of ground squirrels. This suggests the major role of activated macrophages in the arousals of hibernating animals. T lymphocyte proliferation in ground squirrels in the active period is higher than in winter, and the most significant seasonal variations are found in T cell mitogenic response, which increases in spring-summer period. Evidence is presented that functional activity of macrophages of squirrel in autumn has much in common with that in winter rather than in spring-summer period.

Production of Heat Shock Proteins, Cytokines, and Nitric Oxide in Toxic Stress

Expression of heat shock proteins Hsp27, Hsp90, and Hsp70 and production of tumor necrosis factors (TNF-α, TNF-β), interferon-γ (IFN-γ), interleukin-2,-3,-6, and nitric oxide (NO) were studied under conditions of acute and chronic intoxication of animals with lipopolysaccharides. Injection of endotoxin increased expression of heat shock proteins Hsp70 and Hsp90-α in mouse cells. Acute toxic stress also provoked a sharp increase in the production of TNF-α, TNF-β, and NO in mouse cells. The production of other cytokines (interleukins and IFN-γ) was changed insignificantly. In the model of chronic toxic stress, changes in the production of Hsp70, Hsp90, TNF, and NO were followed during 11 days after the beginning of the toxin injections. The expression of Hsp70 and Hsp90 in acute stress was significantly higher than at the final stage of the chronic exposure. The changes in the TNF and NO productions, on one hand, and the production of heat shock proteins, on the other hand, were synchronous. The findings indicate that repeated injections of increasing endotoxin doses result in a decreased ability of the body cells to respond to stress by overproduction of heat shock proteins, TNF, and NO.

Stress response of the cell to exposure to ultraweak electromagnetic radiation.

Studying the molecular mechanisms of cell stress is required for assessing the adaptive capabilities of the cell and the entire organism under exposure to environmental factors. Responses of cells to stress are expressed in a change in the expression of some genes under exposure to certain factors, such as increased temperature, intracellular toxins and other damaging factors, as well as in hypoxia, which may result in denaturation of proteins [1]. Classic markers of stress in the body are some anti-inflammatory cytokines (e.g., the tumor necrosis factor (TNF), interferons, and interleukins) and heat shock proteins, which are involved in the maintenance of cellular homeostasis under adverse environmental conditions. In the past years, the problem of electromagnetic safety has become especially topical because of the active application in human activities of new types of communications and transmitters, including cellular communication.

Involvement of NF-κB transcription factor in the antiinflammatory activity of thymic peptides

484 The thymus is known to play an important role in the normal functions and development of mammals; its state is especially important for the immune system of humans and animals. A number of disturbing fac tors, such as infections, poisons, and ionizing radia tion, have been demonstrated to lead to acute atrophy of the thymic tissue. Accelerated thymolysis is a side effect of some drugs, e.g., for tuberculosis and cancer, which complicates the treatment. Note that all physi ological stress factors, including malnutrition, are supposed to lead to acute thymolysis [1].