Introduction
Inflammation is an immune response that occurs when the immune system encounters harmful stimuli, which emanate from pathogens, irritants, and endogenous substances that can trigger an immune response. Immunologically, inflammation constitutes a non-specific immune response that is characterized by “increased blood flow, elevated cellular metabolism, vasodilatation, the release of soluble mediators, extravasation of fluids, and cellular influx” (1).
Important biomolecules that mediate the process of inflammation are cytokines. Cytokines are special protein molecules that modulate immune responses during inflammation. “Cytokines are secreted mainly by leucocytes and behave as hormone-like proteins that are involved in signaling between cells” (2).
Some of the common cytokines are interleukins, interferons, colony-stimulating factors, and tumor necrosis factors. Since cytokines have different functions in the immune response, proinflammatory cytokines are cytokines that enhance inflammation. The proinflammatory cytokines worsen the inflammation process because they cause unfavorable immune responses that destroy tissues and hinder the healing process. Therefore, this research paper examines the role of cytokines and their mechanism of action during normal immune response and osteoporosis.
Cytokines and Inflammatory Response
Cytokines are protein molecules that modulate inflammatory responses. Usually, cytokines have several functions such as activation of lymphocytes, stimulation of apoptosis, and destruction of pathogens. During the inflammatory response, cytokines activate leucocytes and stimulate the production of cell receptors, which are central in the inflammation process (3). Cytokines can either down-regulate or up-regulate immune responses associated with inflammation; hence, the existence of anti-inflammatory and proinflammatory cytokines. Tumour necrosis factor-β is an example of an anti-inflammatory cytokine, while tumor necrosis factor-α is an example of a pro-inflammatory cytokine (4).
Depending on the nature of the inflammation, the immune system can either downregulate or upregulate inflammatory response by secreting certain cytokines. In essence, cytokines are immune switches that function by turning on certain types of immune cells, while turning off others during inflammation. Thus, cytokines modulate immune responses according to the nature of the harmful stimuli that the immune system receives.
The mechanism of cytokine function is complex and multifaceted. Like hormones, cytokines act locally, work at very low concentrations, and are active within a short period. Although they are present in low concentrations, cytokines act at autocrine, paracrine, and endocrine levels. Autocrine action entails the binding of the cytokines to the receptors of the cells that produce them, while paracrine action involves the binding of cytokines to local cells that are near to the cytokine-synthesizing cells (5). Furthermore, cytokines can act through endocrine action by effecting changes in the immune tissues that are far from cytokine-synthesizing cells.
At cellular levels, cytokines induce changes in the cells by acting through specific cell surface receptors. Cytokines can act synergistically or antagonistically depending on their functions or the nature of cell receptors. This means that cytokines are pleiotropic because one type of cytokine can stimulate different cells to perform different functions. As cytokines act through cell receptors, their stimulating or inhibitory functions have cascading effects. The mechanism of cytokinesis is to “modulate inflammatory responses by shifting from Th1, proinflammatory cascades, to Th2, anti-inflammatory healing cascades “(6). Hence, proinflammatory, and anti-inflammatory cascades complete the mechanism of the inflammation process.
Cytokines and Autoimmune Diseases
Cytokines are a part of systemic factors that control bone remodeling. Proinflammatory cytokines such as interleukin-6, interleukin-1, and tumor necrosis factor-α regulate the resorption of bones; hence, they determine the occurrence of osteoporosis. “The accelerated bone loss observed in many inflammatory diseases indicates that localized and systemic increases in proinflammatory cytokines lead to an uncoupling of bone remodeling in favor of bone resorption” (7).
High levels of proinflammatory cytokines contribute to the resorption of bones, which consequently predisposes one to osteoporosis. “Numerous proinflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts, and a shift towards an activated immune profile has been hypothesized as an important risk factor” (8). Therefore, proinflammatory cytokines predispose individuals to osteoporosis because they activate osteoclasts that cause the resorption of bones.
Cytokines cause osteoporosis through the mechanism that leads to the activation of osteoclasts. Osteoclasts are cells that cause the resorption of bones (9). Increased levels of cytokines mainly trigger differentiation of osteoclasts, and consequently bone remodeling and resorption. Modulation of osteoclast functions and osteoclastogenesis are two mechanisms through which cytokines cause osteoporosis (10).
In the mechanism of modulating osteoclast functions, after T-cells stimulate maturation of osteoclasts, tumor necrosis factor binds to its surface receptor (RANK) on the osteoclasts and causes activation of osteoclasts. Similarly, through the osteoclastogenesis mechanism, cytokines stimulate the maturation of T-cells, which in turn activate osteoclast precursors with the help of macrophage-colony stimulating factor. Overall, the two mechanisms lead to the maturation and activation of osteoclasts that cause osteoporosis.
Conclusion
Since cytokines modulate immune responses and contribute to the occurrence of autoimmune diseases such as osteoporosis, their pharmacological regulation is imperative. During inflammation, cytokines levels increase in inflamed tissues and thus activate osteoclasts. Activated osteoclasts then cause resorption of bones, which ultimately leads to osteoporosis. This means that increased cytokines enhance the risk of osteoporosis. Reduction in cytokine levels during inflammation decreases the risk of osteoporosis among the population. Therefore, the use of anti-inflammatory agents is necessary to downregulate cytokines, which normally increase during inflammation.
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