Cytokine response to bacterial translocation in a model of inflammatory bowel diseases in Macaca Mulatta monkeys

Inflammatory bowel diseases (IBD) comprise a heterogeneous group of disorders with various clinical and morphological manifestations representing significant issues in modern medicine. The aim of our study was to reproduce the signs of IBD in Macaca mulatta (Rhesus macaque) by oral administration of sodium dextran sulfate (DSS), and to assess the cytokine response to induced damage of intestinal barrier and translocation of bacterial components to the bloodstream. Mature Macaca mulatta males (n = 5), kept in the monkey breeding facility at the Research Institute of Experimental Pathology and Therapy were selected as the object of this study. Induction of inflammatory bowel disease in Rhesus macaque was carried out by oral administration of 5% sodium salt of sulfated dextran (DSS) (molecular weight of 40 000) at the volumes corresponding to physiological needs of animals. Immunological and molecular biology methods were used to determine cytokines and the microbial translocation markers. The results of the study showed that induction of IBD in Rhesus monkeys leads to a regular increase in the serum marker of 16S rDNA translocation from the 2nd day after DSS treatment, reaching maximum values on the sixth day. In parallel with increased bacterial translocation, we have revealed an increase in the cytokine response, i.e., a significant increase in the IL-6 and IFNγ concentrations. The stimulation of cytokine production in response to IBD induction was observed at the early stages, beginning from the 1st day, and reached its peak values on the 2nd to 6th days of exposure. It should be noted that the levels of inflammation markers remained high after the discontinuation of DSS, although they showed a gradual decrease towards the end of the experiment. Hence, a model of chemically induced inflammatory process in Macaca mulatta has been developed, characterized by a distinct, predominantly Th1cytokine profile, accompanied by pronounced microbial translocation. The duration of acute inflammation induced by DSS is comparable to the time required for transition into a chronic form. This model is a potentially valuable tool for further studying the pathogenesis and developing new treatments for IBD.