Evaluation of Salivary Granulocyte-Macrophage Colony-Stimulating Factor, Macrophage Inflammatory Protein and Interleukin-1β Levels in Individuals With Different Periodontal Conditions

Periodontal disease is characterized by various microbial infections caused by only certain microbial species out of the many types of bacteria present in the oral cavity, with progressive destruction of the tissues supporting the tooth.

Gingivitis is an inflammation caused by substances secreted from microbial plaque accumulated in or near the gingival sulcus, in the gingival tissue surrounding the teeth, and develops due to bacterial plaque. Gingivitis, the mildest form of periodontal disease, is a common condition and can usually be easily treated with good oral hygiene. Gingivitis, as defined, is present in 50% to 90% of adults worldwide. It has been observed that untreated gingivitis lesions are often at risk of developing into periodontitis in individuals. Periodontal disease is a disorder that causes loss of attachment in the tissues surrounding the tooth and destruction of alveolar bone. Periodontitis, which is the main cause of tooth loss in adults, is a common health problem. The initial cause of periodontitis lesions is microbial dental plaque, which is organized on the teeth and contains many pathogenic bacteria. Within the microbial dental plaque, Porphyromonas gingivalis (Pg), Tannerella forsythensis (Tf) and Treponema denticola (Td) play a major role in the formation of active periodontitis lesions.

Although the presence of pathogens is necessary for the onset and progression of periodontal disease, this alone is not sufficient. The host immune response is the main driver of the pathologic process. A dysregulated host immune response or imbalance within the microbial community (dysbiosis) may lead to disruption of homeostasis in the periodontium, leading to destruction of the extracellular matrix and alveolar bone loss. In immune-inflammatory processes triggered by the interaction of host and bacteria, excessive release of proinflammatory cytokines such as IL-1, IL-6, IL-8, prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) as well as endopeptidases such as matrix metalloproteinases (MMPs) have been found to cause periodontal destruction.

Inflammation in periodontitis and similar local inflammatory lesions and systemic connective tissue diseases causes an increase in biological mediators such as cytokines, prostaglandins and matrix metalloproteinases (MMPs) in the tissues involved and in the systemic circulation.

Members of the colony-stimulating factor (CSF) superfamily are involved in mammalian myelopoiesis, i.e. the formation of monocytes, macrophages, dendritic cells (DCs) and polymorphonuclear phagocytes (neutrophils and eosinophils). There are three main members of this family: Macrophage (M)-CSF (or CSF-1), Granulocyte (G)-CSF (or CSF-3) and Granulocyte-Macrophage (GM)-CSF (or CSF-2). They were first identified as growth factors capable of promoting myeloid colony formation from bone marrow precursors in vitro. In these three CSFs, the entire structure of phagocytes can potentially be controlled . GM-CSF, as its name suggests, was initially identified as a hematopoietic growth factor due to its ability to induce the differentiation of granulocytes and macrophages in vitro by inducing the proliferation and differentiation of bone marrow progenitor cells. However, it was later seen as a cytokine that acts through a specific receptor on myeloid cell populations such as monocytes/macrophages, neutrophils and eosinophils, activating/differentiating them and having a potential role in inflammation.Data from models of autoimmunity and chronic inflammation using mice lacking the GM-CSF gene or neutralizing monoclonal antibodies (mAbs) suggest that GM-CSF may be an important driver of tissue inflammation and associated pain. Examples include arthritis, EAE (Induced Experimental Autoimmune Encephalomyelitis), cardiovascular disease and lung disease. GM-CSF was one of the first cytokines detected in inflamed human synovial fluid and its biological effects outside the bone marrow vary depending on its location and concentration.