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Head - acad. RAMS |
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Head - acad. RAMS |
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Acad. Petr N.Veselkin
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e-mail: korneva@VK5270.spb.edu Department of general pathology and pathological physiology is one of the oldest departments of the Institute of experimental medicine. It was created in 1894. The Head and founder of the department — professor S. M. Lukiyanov who headed the Institute of experimental medicine at that time — invited professor E. S. London in the capacity of his assistant manager in the department. Under the guidance of these two scientists investigations of the pathophysiology of starvation, pathology of the cardio-vascular system were carried on at the department as well as investigations of the mechanisms of the infection process. The works on studying the mechanisms of fever performed under the guidance of academician of the Russian Academy of Medical Sciences P. N. Veselkin who headed the department during three decades (1950-1980) are widely known and enriched the contemporary science with new ideas of the process of the development of fever and its biologically-positive role for organism. One of the merits of the department is an investigation of the biological role of leukocytes in defensive functions of organism. On its basis professor V. E. Pigarevsky has put forward a proposition of a non-phagocytic type of tissue resistance and a conception of a resorptive cellular resistance. A lysosomal-cationic test was proposed for the estimation of the level of antibiotic proteins and peptides in leukocytes (1966-1977).
The whole complex of the results obtained as well as the proposed by E. A. Korneva conception of organization of a multilevel system of neurohumoral regulation of immunological processes in the whole organism became a basis for creation of a new scientific direction — immunophysiology (neuroimmunomodulation, psyconeuroimmunology), with E.A.Korneva becoming one of its recognized leaders. In the Department there are three laboratories:
At present it became evident that the immune system functions are coordinated not only by the nervous system, but the activation of immunological processes influences the work of brain. Investigation of this problem is thought to be perspective and discloses a new layer in the understanding of organization of brain functions and the mechanisms of brain functioning. The brain cells, neurons included, are known to have receptors to the majority of immunomodulating bio regulators — cytokines synthesized mainly by the immune system cells. Many neurons also synthesize these cytokines. One of the main trends in the investigations carried
on at the department of general pathology and pathological physiology is
studying the physiological role of cytokine interleukin-1
and glucocorticoid hormones as mediators of neuro-immune interactions in the
ligand-receptor and signal mechanisms of the development of stress
reaction. An analysis of the intensity of expression of immediate and early response genes — c-fos and interleukin-2 cytokine — was used to investigate the reactions of the immune and nervous system cells to stimuli of different nature. The spatial-temporal pattern of activation of the cells of different structures of the hypothalamus in response to antigenic and non-antigenic effects, introduction of immunomodulating peptide, EHF irradiation of the skin was determined. The morphometrical method of analysis of activated cells expressing the c-fos gene was first used and its informative value was shown. The regularities were found in activation not only of certain hypothalamus nuclei, but also of types of neurons after immunomodulating effects (EHF irradiation of the animal skin). The nearest perspectives are associated with the development of studies of participation of the recently discovered system of the orexin-containing neurons in regulation of the immune system functions. The Department occupies the leading position in Russia in studying the mechanisms of interaction of the nervous and immune systems. These works are widely known abroad.
The data of the primary structures of peptides obtained in these investigations increase our understanding of regularities in the evolution of protective functions of animals. In addition, they make a basis for the development of antimicrobial drugs of new generation for veterinary service and medicine which are highly required now. Rapid growth of bacterial infections resistant to so called "classical" antimicrobial means dictates a necessary search for new therapeutic agents having no structural analogies with antibiotics that had lost their effectiveness. The works of the Department have first demonstrated the stress-protective and immunostimulating effect of defensins and protegrins in vivo suggesting that the functional potential of this group of compound is not limited by antimicrobial activity. All this allows natural antibiotic peptides of animals to be considered as perspective matrix for new drugs of medical purpose with a combination of antimicrobial and immunoprotective properties which can be used for different immunodeficient conditions as protective and regulatory molecules.
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Since
1982 the Department of general pathology and pathological physiology has
been headed by E. A. Korneva — academician of the Russian Academy of
Medical Sciences, Honored science worker of RF, Honoris doctor of the
Institute of experimental medicine, who proceeded with the tradition of
the succession of scientific researches existing at the Institute. She
was the first to put forward and investigate the question of
significance of certain brain structures, hypothalamus in particular, in
regulation of the immune system functions. Department of general
pathology and pathological physiology is a historical and contemporary
centre of immunophysiology in Russia investigating different aspects of
the problem.
Special investigations of the Department are devoted to studying
molecular mechanisms of the interaction of interleukin-1 with target
cells and further intracellular transduction of its signal by the
sphyngomyelin pathway. First experimental grounds were obtained on the
common character of the sphyngomyelin pathway of transduction of the
interleukin-1 signal for the nervous and immunocompetent cells. A
connection of interleukin-1 with the 1 type receptors was found to be
principally necessary for activation of neutral sphyngomyelinase — the
key enzyme of starting up this signal transduction. For the first time
it was shown that the sphyngomyelin pathway of transduction of the
interleukin-1 signal is a common link in the reaction of the CNS cells
and immune system to stress. Priority data were obtained on the
modulating action of glucocorticoid hormones to transduction of the
interleukin-1 signal by the sphyngomyelin pathway. The changed intensity
of transduction of the interleukin-1 signal in the nervous and immune
cells was first demonstrated to be an information indicator of impaired
defensive functions of organism in stress.
The Department of general pathology and pathological physiology is the
leading in Russia center on studying the structural and functional
properties of 
In the Department of general pathology and
pathological physiology under study are the principal, most perspective
directions of pathophysiology of the protective functions of organism
studied at the molecular-genetical, cellular and organism levels. Such a
combined approach allowed revealing the unknown before mechanisms of
neuroimmune interaction of different systems of protection of organism
in the process of realization and regulation of defense functions and
participation of cytokines and antibiotic peptides in theses processes.
Correcting effects of immunoregulating peptides and of the used physical
methods of action (EHF irradiation) were shown. The investigations
carried on in the Department open a possibility in perspective to create
and use new methods of therapy both on the basis of medicines of a new
generation and the application of wave effects (EHF irradiation) in
clinic.