Cytokine regulation of inflammatory processes in respiratory organs of rats exposed to the combined inhalation of chemicals in low concentrations

Introduction. Morphological studies of animals (trachea, bronchi, lungs) exposed to the combined inhalation of chemicals in low concentrations showed the progression of structural changes, indicating the activation of inflammation and fibrosis in the lungs. The role of cytokine markers in developing inflammatory and fibrotic processes and remodeling lung tissue has been studied.

Materials and methods. Male rats (180-200 g) were exposed to a mixture of chemicals (acetone, acetaldehyde, benzene) in low concentrations of 0.7-1.5; 0.9-1.4; 0.2-0.4 (mg/m³), respectively. The concentrations of IL-6, IL-10, IL-1b, IL-4, TGFβ₁, TNFα cytokines (pg/ml) have been measured in the lung homogenate by enzyme-linked immunosorbent assay (ELISA). Microscopic anatomy of the lungs, tracheal wall, bronchi has been studied on the 30^th day of exposure and the 15^th and 90^th days of the recovery period. 

Results. An increase in interleukin-4 and transforming growth factor TGFβ₁ in the homogenate of the lung tissue was shown. An increase in lymphatic follicles, the number of lymphocytes, neutrophils, macrophages, and focal accumulations of eosinophils has been observed in the tracheal wall. In lymphoid infiltrates of the lung tissue - eosinophils, macrophages, and plasmocytes. Accumulation of eosinophilic exudate has been observed in some alveoli. The 90^th day of the recovery period is characterized by a significant increase of TGFβ₁ in the lung tissue, indicating fibrosis, as evidenced by the rise in the number of fibroblasts between the alveoli in the atelectasis zones of lungs.

Conclusion. The chronic combined exposure to the mixture of chemicals in low concentrations is accompanied by a pro-inflammatory process in the lungs with the type II hypersensitivity and increasing IL-4 and TGFβ₁ (a key mediator of profibrotic activity).