Dynamics of alterations in white blood cell and sepsis-associated humoral factors during sulfur mustard intoxication

Introduction. Sulfur mustard (SM) is an important chemical warfare agent. Lack of antidote and pathogenetic means in the arsenal of modern medicine for the treatment of SM poisoning requires further studies on the pathogenesis and development of protective medical devices and treatment schemes. The aim is to assess the features of immune response and intestinal bacterial translocation during SM intoxication. Materials and methods. The experiments were performed with Chinchilla male rabbits. SM was injected to laboratory animals intramuscularly at a dose of 63 mg/kg, amounting to 1.0 LD84. The test materials presented by blood samples collected by cardiac puncture and from the lateral ear vein. Cardiac blood was used to produce serum and subsequently to determine the level of the sepsis-associated humoral factors (lipopolysaccharide, sCD14, procalcitonin, TNFa, IL-6, IL-10) by using enzyme-linked immunosorbent assay. Results. In the peripheral blood of rabbits there were found changes characterized by decreased total leukocyte count, a development of lymphocytopenia and monocytopenia, as well as two-phase granulocyte count dynamics. The blood leukocyte formula showed the most significant changes related to three cell subsets: segmentonuclear neutrophils, lymphocytes and plasmocytes. The analysis of blood serum for assessing level of the sepsis-associated humoral factors showed that the earliest pathobiochemical change was related to higher sCD14. On day 2 post-exposure, a simultaneous increase in the levels of TNFa, IL-6, IL-10 was reported. The cytokine level was decreasing to baseline range starting from day 3 onwards, whereas the clinical manifestation of SM intoxication was increasing and reaching the maximum magnitude. The analysis of blood serum for lipopolysaccharide level showed its increase on day 3 and 4 post-exposure. Conclusion. The study data in the context of the proposed interpretation, allow to highlight the following phasing of pathological changes during an extremely severe SM intoxication: day 1 — myeloid phagocytic system activation and hyperphagocytosis; day 2 — systemic inflammatory and compensatory anti-inflammatory response syndromes; days 3–4 — “immune paralysis”, intensified bacterial translocation, depletion of the endotoxin-binding system and “endotoxin aggression”.