Study of chondroprotective properties of interleukin-1 receptor antagonist.

Abstract

Osteoarthritis is one of the most widespread diseases, represents a medical and socio-economic problem and is one of the first places among the causes of long-term disability of the population in the world. Cytokine mechanisms of osteoarthritis development are attracting more and more attention. The aim of the study was to determine the chondroprotective and anti-inflammatory properties of the original recombinant interleukin-1 (IL-1) receptor antagonist (ARIL-1) raleukin on the model of systemic steroid osteoarthritis (SSO) in rats. Materials and methods. The SSO model was reproduced in a modified form by intramuscular three-time administration of dexamethasone at a dose of 7 mg/kg with an interval of one week. Raleukin was injected subcutaneously in a conditionally effective dose of 3 mg/kg for anti-inflammatory activity, and glucosamine (GA) orally in a dose of 50 mg/kg (ED50 for anti-inflammatory activity). Starting from the 28th day of the study and for 4 weeks, the study objects were introduced by the appropriate route once a day. Result. The results of the experiment show that clinical signs of damage to the locomotor system appeared in all animals after three administrations of dexamethasone. Later and before the end of the experiment, a typical clinical picture of the development of SSO was observed, which was confirmed by the results of the study of biochemical markers (mainly in blood serum) of the state of the connective tissue of the experimental animals. Significant changes in the functional status of the animals were noted in rats with SSO who received raleukin starting from the second week of administration. In rats, motor activity increased, tolerance to physical exertion increased, joint condition visually normalised, and appetite increased. When the reference drug GA was administered, the functional state of the animals differed from the control pathology group to a somewhat lesser extent. Besides, raleukin did not reliably differ from GA in its effect on biochemical parameters characterising the state of connective tissue and the content of its main metabolites in the blood serum of rats with steroid osteoarthritis. Conclusions. In the model of systemic steroid osteoarthritis, raleukin contributed to the improvement of functional indicators of the condition of animals and the normalisation of their body weight; namely, it moderately reduced the content of all markers of connective tissue metabolism in the blood serum of animals, especially chondroitin sulfates and sialic acids, which can be explained by the systemic nature of its effect. In terms of its effect on the level of the main metabolites of connective tissue in the blood serum of rats, raleukin prevailed over glucosamine hydrochloride. Thus, the analysis of biochemical data against the background of experimental osteoarthritis allows us to draw a conclusion about the high chondroprotective and anti-inflammatory potential of the recombinant IL-1 receptor antagonist