Inflammation: Page and Schroeder 1976 Model

[Check out my post on the Page & Schroeder periodontal lesion]

The original study

The Page and Schroeder 1976 study described the progression of periodontal inflammation from gingivitis to periodontitis but did not try to explain why. At that time the exact mechanism involved in the establishment of gingivitis and subsequently periodontitis were not well-known. Recent findings well integrate with the classical model of Page and Schroeder and explain, even if still not completely, how the chain of the events take place.

Inflammation. (via

The cascade in few words

Innate factors such as complement, resident leukocytes, and especially mast cells play an important role insignaling endothelium, thus initiating inflammation. Acute inflammatory cells protect local tissue by controlling the periodontal microbiota within the gingival crevice and junctional epithelium (neutrophils). If triggered, chronic inflammatory cells, macrophages and lymphocytes protect the entire host from within the subjacent connective tissue and do all that is necessary to prevent a local infection from becoming systemic and life threatening including the sacrifice of local tissue.

Health vs Disease

Integrating classical and recent findings

The two authors (Page & Schroeder 1976) described the characteristics of the initial lesion as dilatation of arterioles and increased permeability, inflammatory infiltrate rich in PMN and initial collagen loss. These findings could be explained by the following cascade of events.

  • Colonization of the gingival sulcus by the bacterial plaque, this triggers the innate immune system, the complement, in particular the release of C3a and C5a, that stimulate vascular changes by degranulation of mast cells that were residents in the tissue.
  • The degranulation of mast cells release cytokines (TNF-α, TGF-β, IL-4, IL-6, IL-1, IFN-γ) that act on different levels: stimulate endothelial cells to release chemokines that attract leukocytes to the area.
  • The first cells to appear in the infiltrate are the neutrophils. This is the dominant cell type in the epithelium thanks to IL-8 and ICAM- 1 that mediate their migration from connective tissue to junctional epithelium. The neutrophils play a major role in the initiation and development of the periodontal lesion, and disorder in neutrophils are associated with periodontal infections and aggressive periodontitis. Neutrophils show affinity for C3 and IgG and phagocytize the bacteria invading the host.
  • The degranulation of these bacteria releases phospholipids of the bacterial wall in the tissue that is the fuel of the arachidonic acid cascade and will result in increased production of prostaglandins (involved in activation of osteoclasts and responsible for bone remodeling).
  • The production of chemokines by resident cells and neutrophils continues and finally antigen presenting cells (macrophages and B cells) reach the area. This cells bring antigen to the lymphnodes were formation of IgG is initiated. These cells dominate the established and advanced lesion as described by Page and Schroeder.

Photomicrograph of junctional epithelium (dark pink) and connective tissue (light pink).

Another important feature of the advanced lesion is the formation of the periodontal pocket and the transformation of the junctional epithelium into pocket epithelium. This process involves proteinases (MMP, elastase, cathepsin G) expressed by neutrophils, macrophages, fibroblasts, epithelial cells, osteoblasts and osteoclasts, but also by bacteria such as AA and PG. This mediators are involved in the destruction of the collagen fibers surrounding and limiting the junctional epithelium and allow the apical and lateral proliferation of the latter. The intense infiltration of neutrophils in the junctional epithelium is also believed to be involved in the formation of the pocket. The weight of the neutrophils themselves could detach the junctional epithelium from the tooth surface and thus create the pocket.

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