Accurate Education – Pathophysiology of Chronic Inflammation

Most of the features of acute inflammation continue as the inflammation becomes chronic, including the expansion of blood vessels (vasodilation), increase in blood flow, capillary permeability and migration of neutrophils into the infected tissue through the capillary wall (diapedesis). However, the composition of the white blood cells changes soon and the macrophages and lymphocytes begin to replace short-lived neutrophils.

Thus the hallmarks of chronic inflammation are the infiltration of the primary inflammatory cells such as macrophages, lymphocytes, and plasma cells in the tissue site, producing inflammatory cytokines, growth factors, enzymes and hence contributing to the progression of tissue damage and secondary repair including fibrosis and granuloma formation, etc.

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Immune Cells

In response to foreign or self-antigens, the tissue immune cells such as macrophages and dendritic cells release cytokines such as IL-1 and TNF-α. These cytokines induce the injury-site-endothelial cells to release Selectins and Integrins which stimulate chemotaxis and diapedesis of the circulating leukocytes. In addition to the recruitment of leukocytes, the tissue macrophages, and dendritic cells also play a role in the clearing of the antigen by phagocytosis, the release of cytokines and serving as antigen-presenting-cells to lymphocytes.

Once the circulating leukocytes enter the local injury site, they are activated by various cytokines and chemokines secreted by the macrophages and dendritic cells. On activation, the leukocytes further release cytokines and mediators of inflammation.

Neutrophils

Neutrophils are the initial cells and most predominant in the acute phase of inflammation. Neutrophils contain granules rich with lysozyme, matrix metalloproteinases, myeloperoxidase which are released on the foreign or self-antigen leading to its destruction. Neutrophils also destroy the antigen by phagocytosis, the release of reactive oxygen species and cytokines such as IL-1, IL-6, and TNF-α.

Lymphocytes

Lymphocytes including T-lymphocytes and B-lymphocytes are the next line of defense, and they play a crucial role in mediating inflammation by several complex mechanisms including secreting of cytokines, co-stimulation of lymphocytes, and production of antibodies and immune complexes.

Platelets

Circulating platelets can also play a role in inflammation by platelet aggregation, thrombus formation and degranulation releasing chemokines and inflammatory mediators.