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close this bookCauses and Mechanisms of Linear Growth Retardation (International Dietary Energy Consultative Group - IDECG, 1993, 216 pages)
close this folderThe effects of the inflammatory response on bone growth
View the document(introductory text...)
View the document1. Systemic changes in inflammation - The acute phase response
View the document2. Local changes in inflammation
View the document3. Mediators of local changes-eicosanoids
View the document4. Mediators of local changes - Cytokines
View the document5. Interleukin-1 (IL-1)
View the document6. Tumour necrosis factor (TNF)
View the document7. Interferon gamma (IFN?)
View the document8. Interactions of osteotropic influences
View the documentReferences
View the documentDiscussion

Discussion

Until now, experimental work on growth plates has mainly concentrated on the characterization of processes going on in a normal growth plate, rather than on systematic changes of conditioning factors; one therefore has not yet identified the dominant processes in relation with the growth plate that are either enhanced or reduced by inflammatory processes.

Various proteins and protein inhibitors play an important role in the inflammatory response, which is therefore modified in children suffering from protein-energy malnutrition. It can be hypothesized that, to mount an adequate inflammatory response, not only quantitative requirements for protein but also for specific amino acids have to be met. Looking for instance at the amino acid composition of acute phase proteins, one can speculate what the requirements for these might be for an acute phase response, but the experimental work to test this hypothesis has not yet been done.

Different cells involved in bone formation and growth have different metabolisms and nutritional substrate requirements. Osteoclasts for instance are quite different from other bone cells insofar as they use a fatty acid oxidative process to meet their energy requirements.

Essential fatty acids of the omega-6 and omega-3 type affect growth in animal studies. Traditionally, only omega-6 fatty acids have been considered necessary for humans, but recent evidence suggests that omega-3 fatty acids are also essential for normal brain growth and development. Low levels of arachidonic acid in formula fed preterm infants were associated with decreased weight and length gain in the first year of life.

The same seems to be true for cells involved in the inflammatory response. Monocytes, that produce and secrete cytokines, are activated by essential fatty acids. In osteoporotic women who were treated by hormone replacement therapy, changes in cytokine secretion from monocytes were observed.

The inflammatory response can exert an effect on growth via hormones acting not only locally, but also systemically. Cortisol, for instance, has a catabolic effect on the growth plate, and hepatic IGF-I production drops dramatically as part of the acute phase response. Unfortunately there is as yet little information on the range and intensity of these responses to different types and severities of infection. The experimental work done so far has usually been on a few clearly defined and fairly strong challenges to the system. We need to know more on effects of common types of low-level infections and on whether they still produce an inflammatory response that is sufficient to affect bone growth. Scientists working on cytokines have been focusing their attention primarily on effects on immune responses and not on growth.