Host modulation

As discussed in previous chapters, periodontal disease progression is associated with subgingival bacterial colonization and biofilm formation.  This microbial biofilm elicits a host response, with resultant osseous and soft tissue destruction. In response to endotoxins derived from periodontal pathogens, various inflammatory chemical mediators are released by the host cells. The immunoinflammatory response has been described as a ‘‘double-edged sword’’, and besides providing specific antibodies and polymorphonuclear neutrophils (PMNs), that represent the dominant natural factors responsible for control of the bacterial challenge, it initiates the destruction of the connective tissue 1. Page et al. (1997) 2, stated that periodontal destruction in periodontitis is the result of connective tissue-degrading mediators such as, matrix metalloproteinases (MMPs) and inflammatory mediators (prostaglandins, interleukins) that occur as a part of the inflammatory response. There is a vital balance between pro and anti-inflammatory chemical mediators in healthy tissue. When the pro-inflammatory mediators increase, tissue destruction results. The purpose of host modulation therapy is to restore this balance.

Basic concept of host modulation

Host modulation is a therapy that is targeted at the host response. As already stated, the result of the host-bacterial interaction is the release of various inflammatory mediators that cause tissue destruction. Using various therapeutic agents that can downregulate or inhibit the production, activation or biological function of the pro-inflammatory mediators is the basic mechanism of action of host modulation therapy.

Definition of host modulation

The definition of the host from a medical dictionary reads ‘‘the organism from which a parasite obtains its nourishment or in the transplantation of tissue, the individual who receives the graft’’. The definition for the term modulation is ‘‘the alteration of function or status of something in response to a stimulus or an altered chemical or physical environment’’ 3.

The inflammatory response in periodontal disease includes the activation of leukocytes, neutrophils, T-lymphocytes and plasma cells. Subsequently, various chemical mediators are released by these immune competent cells, which along with providing a defense to the host also degrade the host connective tissue.

Our present understanding of the pathogenesis of periodontal disease has led to the development of host modulation as a treatment strategy that can be used in addition to conventional treatment approaches. This therapy acts on the host part of the host-microbial interaction. Host response modulation refers to the downregulating destructive aspects of the host response so that; the deleterious effects of various inflammatory mediators on the host tissues are reduced.

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Historical background of host modulation therapy (HMT)

Golub 4, 5 and Williams 6 are considered to be the pioneers in the field of HMT in periodontics. While working on diabetic rats, in which there is an excess of collagenase activity, they observed improvement in the gingival health of rats treated with a tetracycline. Since, they were working on germ-free rats and the gingival inflammation, therefore, could not have had a bacterial etiology, the investigators concluded that the improvement was most likely due to tetracycline inhibition of the host-derived enzyme collagenase. Collagenase is one of the MMPs that mediate connective tissue breakdown and plays an important role in the pathogenesis of periodontal diseases. These findings founded the basis for host modulation therapy.

Pathogenesis of periodontal disease progression

As already discussed in previous chapters, periodontitis is a complex disease in which disease expression involves intricate interactions of the biofilm with the host immunoinflammatory response and subsequent alterations in bone and connective tissue homeostasis 7-9. Periodontal diseases have a well-defined bacterial etiology. Along with that, the present data suggest that environmental factors, acquired risk factors, and genetic risk factors play an important role in the pathogenesis of periodontal diseases. Kornman (1999) 1 proposed a model of periodontal disease pathogenesis that explains how the host-parasite interactions takes place and leads to the disease progression (Figure 13.1).

Model of periodontal disease pathogenesis

Periodontal disease progression

The host response is characterized by the production of host-derived inflammatory mediators, including cytokines and lipids by neutrophils, monocytes, lymphocytes and fibroblasts. As periodontal diseases are multifactorial diseases, environmental risk factors, such as diabetes mellitus, cigarette smoking, and stress, as well as genetically transmitted traits, such as interleukin-1 (IL-1) gene polymorphisms, may accentuate the host inflammatory response to the bacterial challenge and, eventually, the susceptibility to the disease 10. One of the most important consequences of this host response is the generation of matrix metalloproteinases (MMPs), which seems to be highly related to tissue destruction and remodelling events in periodontal diseases 11.

Rationale behind host modulation therapy

HMT is directed on the host side of the host-microbial interactions. It is clear from the present evidence that host response is responsible for most of the tissue breakdown during the host-microbial interaction. HMT provides us the opportunity to modify the host immune response in such a way that tissue destruction is minimized. However, it must be emphasized here that HMT doses not stops the normal defense mechanisms, but instead, it amends the excessively elevated pro-inflammatory mediators to enhance the opportunities for wound healing.

When to give host modulation therapy

As we know that bacterial challenge is the primary etiological factor in the development and progression of periodontitis. Many studies have clearly demonstrated that reduction in microbial load leads to the reduction in inflammation in periodontal tissues. But, many patients do not respond appropriately to the conventional periodontal therapy and the periodontal tissue breakdown continues. Present data strongly suggest that an abnormal immune response, genetic factors, environmental factors and patient’s systemic condition are responsible for the degree and magnitude of periodontal destruction. Studies have demonstrated that patients with generalized aggressive periodontitis have an excessive immunoinflammatory response 12, 13. Patients suffering from insulin-dependent diabetes have been shown to have high gingival crevicular fluid levels of PGE2 and IL-1β even in periodontal sites with minimal inflammation 14. IL-1β polymorphism is an important factor that contributes to the abnormal immune response in certain individuals.

So, it becomes clear from the above description that individuals who are at high risk for development of severe periodontitis should be given host modulation therapy. These include smokers, diabetics, and those who are positive for the IL-1 genotype.

Host response therapeutics for periodontal diseases

Various agents which can modulate the host immune response have been introduced and tested for their efficacy. These agents may modulate the immune response by a variety of mechanisms. These include inhibition of prostaglandin inhibitors, cytokine inhibitors, MMP’s inhibitors and bone resorption inhibitors. A detailed description of these agents has been given in the next chapter.


Host modulation therapy has become an important modality of treatment for periodontal diseases. However, this therapy is an adjunct to the conventional periodontal treatment. Furthermore, this therapy is not indicated in all the patients and should be used after a thorough evaluation of the patient.

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Periobasics: A textbook of periodontics and implantology

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