T. V. Gavrilova

The effect of MP-3 on mouse peritoneal macrophage respiratory boost activity and production of IL-1β and TNF-α under in vivo stress

153 Myelopeptides are a group of bioregulatory mole cules of a peptide nature displaying a wide range of immunoregulatory activities owing to a targeted action of individual peptide fractions on various com ponents of immunogenesis [1]. So far, six individual myelopeptides (MP 1, MP 2, MP 3, MP 4, MP 5, and MP 6) have been isolated from the supernatants of bone marrow cell cultures; these myelopeptides dif fer from one another in the direction and target of their action [2]. The most important problem in cur rent immunology is development of the methods for targeted immune correction in inflammatory pro cesses of various origins and immunodeficiency states. One of the major causes of the latter is the stress with damages of the immune system functions as a leading contributor to pathogenesis. We have earlier demon strated that MP 1, MP 3, MP 5, and MP 6 inhibit a PHA induced lymphocyte proliferative response and LPS induced IL 1β production, as well as zymosan induced generation of reactive oxygen species and in vitro production of IL 1β and TNF α [4, 5]. It is important to estimate the immunomodulatory effects of the hexapeptide MP 3 (Leu Val Cys Tyr Pro Gln), involved in modulation of innate immunity cell functions, under in vivo immobilization stress.

Effects of myelopeptides on immune response and morphometrical manifestations of inflammation in experimental penetrating wound of the eye

Myelopid and MP-1 myelopeptide increase the count of antibody-producing cells, reduced under the effect of injury and standard therapy, and do not modify the suppression of delayed hypersensitivity. Injections of myelopid and MP-3 together with standard drugs optimized the traumatic inflammation processes.

Myelopeptides in treatment for stress- and injury-induced changes in the immune response to a heterologous thymus-dependent antigen in rats with penetrating eye wounds

3. Throughout the text of the article LOR should read DTH. Erratum: “Myelopeptides in Treatment for Stressand InjuryInduced Changes in the Immune Response to a Heterologous Thymus-Dependent Antigen in Rats with Penetrating Eye Wounds” [Doklady Biological Sciences, 2007, vol. 412, pp. 8–10] T. V. Gavrilova, N. L. Berkasova, Yu. I. Shilov, M. V. Chereshneva, and Academician V. A. Chereshnev Submitted April 5, 2007; accepted for publication April 15, 2007

Regulation of the peritoneal macrophage functional activity by the MP-5 and MP-6 myelopeptides under stress

In mice, two-hour immobilization stress inhibited zymosan-induced production by macrophages of the oxygen radicals and cytokine IL-1β. After myelopeptides MP-5 and MP-6 were administered into mice, the stress-induced inhibition of the reactive oxygen species (ROS) and IL-1β was abrogated. MP-5 peptide stimulated spontaneous ROS production by macrophages and reduced IL-10 production under stress. Thus, under in vivo conditions and under stress, the effect of MP-5 and MP-6 myelopeptides modulates the peritoneal macrophage activity.

The effect of polyoxidonium on immune response and morphological parameters of inflammation after experimental penetrating eye injury

75 Unique physiological features of the organ of vision and its immune status make penetrating eye injury (PEI) and its therapy a multidisciplinary problem [1–3]. PEI is an example of local injury inducing both loñal responses with the disruption of immunosuppression in the organ and general changes in the immune syss tem [1, 4]. The Russian immunostimulant Polyoxidoo nium is a promising drug for enhancing healing proo cesses in the injured eye tissues, formation of more mature and structured scar tissue [5, 6]. This study has provided evidence for the antiiinflammatory effect of Polioxidonium and its ability to attenuate inflammaa tory cell infiltration in the injured area. We have demm onstrated that, despite stimulation of secretion of antii bodies, the traumatic immunosuppression of the delayeddtype hypersensitivity response (DHR) to thyy mussdependent xenoantigen occurs shortly after the injury. This offers new prospects in discovering the mechh anism of the immunomodulation effect of this drug. The study was performed on 119 white male rats weighing 213 ± 4 g. Penetrating injury of the right eye was inflicted under 2% procaine anesthesia [6]. On the first stage of the study, the immunomodulation effect of polyoxidonium alone or together with standard therapeutic protocol for PEI during immune response to sheep erythrocytes was evaluated. The injured anii mals were divided into four groups (Table 1). The fifth group included control animals (the PEI was not inflicted, while the right eye was sham anesthetized with 0.9% NaCl). All drugs were administered 6 h after the injury. Standard therapeutic drugs were adminiss tered subcutaneously (0.1 mg/kg dexamethasone phosphate once a day; 0.5 mg/kg sodium diclofenac, 12.5 mg/kg sodium ampicillin, and 1.5 mg/kg gentamii cin sulfate twice a day). Polyoxidonium (0.1 mg/kg) was administered 6 h, two days, and four days after the injury. To induce the immune response, all rats were sensitized with sheep erythrocytes (10 8 cells subcutaa neously in the right foot sole) 7 h after the beginning of the experiment. On day 4, the antigen was adminiss tered subcutaneously (10 9 sheep erythrocytes in the right sole, and 0.1 mL of 0.9% NaCl in the left sole). On day 5, all animals were anesthetized with ether and decapitated. The endocrine response was evaluated by the number of antibodyyforming cells in the regional (popliteal) lymph node, which was evaluated by local hemolysis in agarose gel [7]; the DHR was evaluated by the response index [8]. …

Proliferative response of lymphocyte to pokeweed mitogen depends on the concentration of endogenous cortisol in the early post-traumatic period in patients with penetrating eye injury.

The intensity of lymphocyte proliferation in response to pokeweed mitogen depends on cortisol level in the peripheral blood in the early post-traumatic period of penetrating eye injury. Lymphocyte proliferation in 72- and 96-h cultures from patients with high levels of endo genous hormone was suppressed. In 120-h cultures, the intensity of proliferation remains unchanged. Lymphocyte blast transformation was increased in 120-h cultures from patients with normal cortisol concentration and remained unchanged in case of low cortisol level.

Expression of TLR9 and BD-2 protein genes in corneal cells of mice of different strains with herpetic keratitis.

The dynamics of gene expression of two proteins, TLR9 (one of the key receptors recognizing CpG repeats of herpes virus DNA) and β-defensin 2 (antibacterial peptide), was studied on the model of herpetic keratitis in C57Bl/6 and BALB/c mice. New data on differences in TLR9 gene expression in mice of the two strains infected with the virus were obtained. Reduced TLR9 gene expression in the cornea of C57Bl/6 mice was associated with their high sensitivity to infection caused by herpes simplex 1 virus.

Dependence of the lymphocyte proliferative response on the endogenous cortisol level and sensitivity to β-adrenergic regulation in vitro in the early period of penetrating eye injury

304 Penetrating eye injury (PEI) is an example of spa tially limited injury entailing not only local responses, including impairment of immunosuppression mecha nisms in this immunologically privileged organ itself, but also systemic stress related changes in the immune system in response to the hazard of the loss of an organ important for receiving information [1–3]. The mech anisms of these changes in PEI have not been studied sufficiently; most researchers consider the anterior chamber associated immune deviation (ACAID) to be the leading phenomenon [4–6]. We have obtained pioneering data on the role of glucocorticoids and the change in the sensitivity of the lymphocyte prolifera tive response to β adrenergic regulation caused by these hormones in the T cell response to mitogens during the early period of PEI. This offers new possi bilities for clarifying the role of the neuroendocrine system in the modulation of immune functions in PEI.

Mechanism underlying the effect of myelopeptides on lymphocyte proliferation in vitro.

We studied the role of monocytes in the effect of myelopid and myelopeptides MP-1, MP-3, MP-5, and MP-6 on functional activity of peripheral blood lymphocytes in the reaction of blast transformation. Myelopeptides MP-1, MP-3, and MP-6 suppressed blast transformation of lymphocytes. The effect depended on the presence of monocytes in a cell culture.

Effects of Myelopidum and Myelopeptides MP-5 and MP-6 on Lymphocyte Proliferative Response

Bone marrow peptides (myelopeptides) belong to a group of regulatory peptides isolated from the supernatant of bone marrow cell cultures [1]. These substances exhibit a wide spectrum of immunoregulatory activity; the drug myelopidum, a mixture of native myelopeptides, has been developed on their basis. Six individual peptide preparations obtained by fractionation have been shown to have independent and selective immunomodulating effects [2]. The first four of the six myelopeptides (MP-1, MP-2, MP-3, MP-4, MP-5, and MP-6) are now the best studied, whereas the regulatory role of the remaining two is still unclear.