Interleukin Local Therapy
Development of the Local Interleukin-1 Therapeutic Strategy and Study of the Mechanisms of Interleukin-1 Biological Activity after Local Application
Tech Area / Field
8 Project completed
Senior Project Manager
Gremyakova T A
Institute of Highly Pure Biopreparations, Russia, St Petersburg
- Faculdade Medicina Lisboa/Hosp.Sta.Maria, Portugal, Lisbon
The aim of the project is to develop local interleukin-1 (IL-1) therapeutic strategy and to study mechanism of IL-1 antiinfectious, immunostimulatory and wound-healing activity after local application in humans.
IL-1 is one of the main mediators for development of the immune and acute-phase responses. IL-1 possesses a wide spectrum of biological activity including activation of leukocytes, stimulation of differentiation and functional activity of immunocompetent cells, enhancement of proliferation of hemopoietic precursors, stimulation of connective tissue metabolism, activation of neuroendocrine system. Experimental studies showed that IL-1 has high immunostimulatory activity. The goal of the modern immunotherapy is to use IL-1 biological potential to treat human diseases connected with the immune system disorders, especially in the cases when immune system can not provide adequate response to invading pathogens. Unfortunately, systemic IL-1 application may not be very effective because of various adverse effects of IL-1 in humans due to a short distance between therapeutically effective and toxic doses. Alternatively IL-1 can be applied locally directly to the inflammatory site for stimulation of defense mechanisms. In some experimental studies it has been shown that when applied to the area of pathogen penetration IL-1 can cause local immune stimulation through induction of interferon production, neutrophilic leukocyte stimulation, activation of endothelium, enhancement of endogenous cytokine synthesis. All these activities may be beneficial for the host defense against various viruses, bacteria and fungi. Except of this IL-1 can stimulate wound healing by activation of fibroblasts.
The main goal of the project is the development of local IL-1 treatment methods where recombinant human IL-1 could be applied directly to the inflammatory site. In this way IL-1 probably may be administered at doses that will give high local concentration and allow to develop strong immunostimulatory activity. On the other hand these doses will be too small to give systemic IL-1 adverse effects.
At present, human recombinant IL-1б, IL-1в and IL-1 receptor antagonist are cloned and available for experimental studies, as well as monoclonal antibodies and home-made ELISA test-systems for measuring human IL-1, IL-8 and tumor necrosis factor (TNF). There is an experience of studying local and systemic changes in immune system using various experimental models and in patients with inflammatory disorders. Human recombinant interleukin 1в produced in the Institute of Highly Pure Biopreparations is approved by Russian National Pharmacological Committee for use in clinical practice.
The work on this project includes:
- studying IL-1в local application strategy in different animal models of local infections and wound healing;
- investigating the IL-1 and some other cytokine levels during the development of different types of inflammatory disorders in humans;
- conducting clinical trials of IL-1в preparation for therapy of local bacterial pyogenic infections (lung abscesses, pleural empyemas, rhinosinusitis, cutaneous phlegmons, etc.), skin trophic ulcers, burns and surgical wounds, especially infected;
- studying mechanisms of IL-1 immunostimulatory and wound healing activity (local cytokine production, leukocyte functional activity, change in cell composition).
The studies on the project are related mainly to applied research. However, a part of them is also related to basic research. The work on this project will allow:
1. To obtain data on both the participation of cytokines, particularly IL-1, in regulating local inflammation and the mechanism of IL-1 biological effect during local application.
2. To develop new therapeutic approach for the local IL-1 application in treating several inflammatory diseases that will fully avoid systemic toxicity and may be further applied in clinical practice.
The present project responds to the ISTC objectives because it is directed to development and introduction of new methods and medical preparations for local therapy of widely spread inflammatory diseases in clinical practice. The results of the project may also contribute to solution of international and country national problems related to treatment of inflammatory diseases and skin lesions.
The specialists have a significant positive experience working with ISTC.