Simvastatin and Recombinant Antagonist of Receptors of Interleukin-۱ Modulate Toll-like Receptors in Experimental Acute Ileitis in Rat

Background: The pathogenesis of inflammatory bowel disease is complex and multifactorial. Studies have led to the current concept that Toll-like receptors represent key mediators of innate host defense in the intestine, and they are involved in maintaining mucosal as well as commensal homeostasis. We studied the possibility of simvastatin and antagonist of receptors of interleukin-۱ for pharmacological correction of acute ileitis in rats with a focus on the expression intensity studies of TLR۲ TLR۴ with lymphocytes of small intestine. Materials and Methods: Experiments were carried out on male Wistar rats aged ۵–۷ months (body mass ۲۶۰–۲۸۵ g). Rats were divided into four experimental groups: group ۱ ― control group ۲ ― rats with indomethacin-induced ileitis group ۳ ― the rats were given simvastatin (۲۰ mg/kg, for ۵ days, subcutaneously) group ۴ ―the rats had given antagonist of receptors of interleukin-۱ (۳ mg/kg, for ۵ days, subcutaneously). The TLR۲ and TLR۴ immunopositive lymphocytes were determined using a direct immunofluorescence technique using a monoclonal rat antibody. Results: We established that development of ileitis was accompanied with the change of amount of TLR۲+ and TLR۴+ lymphocytes and the density of TLR۲, TLR۴ in immunopositive cells. Drug administration during the development of experimental pathology was accompanied by changes in the expression of TLR۲, TLR۴ and their density on lymphocytes. Conclusions: Simvastatin and antagonist of receptors of interleukin-۱ seemed to be beneficial in indomethacin-induced rat ileitis model through modulate TLR۲ and TLR۴ expression with lymphocytes of small intestine.

Keywords:

Ileitis , Recombinant antagonist , receptors of interleukin-۱ (ARIL-۱) , Simvastatin , Toll-like receptor