Influence of the associative relationship between copper and cytokine status on the formation of nutritional immunity in patients with tick-borne rickettsiosis caused by Rickettsia heilongjiangensis

The Far East is distinguished by high rates of tick-borne rickettsiosis (TBR), which is dominant among all natural focal infections. It is important to note that the etiological agent of TBR in Khabarovsk Territory is R. heilongjiangensis. In general, in the region in the period 2022–2023, a pronounced upward trend in incidence was revealed (by 55.85 %), amounting to 25.08 per 100 thousand people. A detailed study of individual links in the pathogenesis of TBR caused by a new endemic pathogen remains relevant in the search for associations of significant biomarkers in order to assess the severity and prognosis of the disease. Purpose of the study. Evaluation of the relationship between the level of copper (Cu) and individual elements of the cytokine status in the blood serum of patients with TBR caused by R. heilongjiangensis, to understand the issues of immunity formation, and in particular, the participation of nutrients in this pathophysiological process. The levels of serum Cu and some proinflammatory (IL-2) and anti-inflammatory (IL-4) cytokines were analyzed in patients with moderate CR, taking into account two-time examinations: during hospitalization (at the height of the disease (4-5 days of illness)) and in the early convalescence period (8-10 days from the onset of the disease). It was found that at the height of the disease, a statistically significant increase in the serum Cu level was observed (1.8 times, p<0.000009), which was combined with a significantly pronounced activation of the endogenous mediators studied (IL-2 – 1.7 times, IL-4 – 1.7 times, p<0.05). The correlation analysis revealed a weak unidirectional reliable relationship between the Cu level and the IL-2 cytokine during the peak of the disease (r=0.3132, p<0.05) and a significant multidirectional relationship between the Cu and IL-4 content during the recovery period (r=-0.5709, p=0.0086). The obtained results indicate the induction effect of cytokine status elements during inflammation on the generation of a free Cu pool for the purpose of its mobilization as a direct bactericidal agent, and, therefore, it becomes one of the positions of nutritional immunity in patients with CR caused by R. heilongjiangensis.

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