Idiopathic pulmonary fibrosis (IPF) is a cause-unknown interstitial lung disease, where the airways are packed with inflammatory cells and then the alveolar walls and interstitium become fibrotic. On the molecular level, it is a disease of too much parenchymal tissue remodeling and epithelialization, and collagen production. The incidence of fibrosis appears to be strongly associated with the size and location of myofibroblast foci in the inflamed lung. IL-8 is elevated in the bronchoalveolar lavage fluid (BALF) of idiopathic IPF patients, and research is still emerging that it's involved. We have also seen the IL-8 mRNA in AMs of IPF patients. AMs hold IL-8 in their main reservoir in the lower respiratory system. Not only AMs but many other cells – endothelial and epithelial cells, fibroblasts, monocytes, and neutrophils – themselves generated and released IL-8.
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Interleukin 8
Interleukin is a lymphokine that works with white blood cells or immune cells. It's the type of blood cell growth factor. The two coordinate and work in concert to complete the hematopoietic and immune regulation tasks. Interleukin functions as a messenger for information, activation, and modulation of immune cells, activation of T and B cells, proliferation and differentiation, and inflammation. IL-8 is one such chemokine that is involved in inflammatory response by drawing and activating neutrophils and other immune cells. IL-8 is elevated in the IPF patients' BALF. The chemokine IL-8 is a member of the CXC family and a powerful chemoattractant and activator of neutrophils.
Physiological Activity of Interleukin 8
Biological function IL-8 is a multifunctional factor, its biological function is not specific to any species. The target cells it targets are, as we learned very early on, neutrophils. It is able to selectively drive neutrophils into inflammatory tissues, stimulate their degranulation, generate superoxide anions, induce respiratory bursts, engage inflammatory cells, initiate acute phase protein synthesis, induce fever, be involved in inflammatory pathological inflammation, release inflammatory mediators, activate the proliferation of fibroblasts - chronic inflammation, so it is also part of inflammatory response. As research advanced, we learned that IL-8 was able to act on cells of all kinds. It can induce an inflammatory response, induce the formation of blood vessels, induce mitosis, control the host immune system, etc. It is inversely connected with the prevalence and onset of various inflammatory diseases, tumors, and immune disorders.
Fig. 1 The coordination mechanism of IL-8 on lung diseases (Cesta, M., et al. 2022).
Interleukin-8 Regulated Signalling Networks
One is to act as a modulator of neutrophil activation, by activating neutrophils and other immune cells to fly to the infection site to stimulate inflammatory reactions. Second, when immune cells (mostly neutrophils) have reached the area of inflammation, interleukin-8 can plow them down. Protein tyrosine kinases of the interleukin-8 signaling system are studied for cell proliferation and cell survival in tumors and endothelial cells. Interleukin-8 has also been found to activate epidermal growth factor receptors in ovarian cancer and vascular endothelial cells, which in turn activate mitogen-activated protein kinase downstream pathways.
Its signaling mechanisms in interleukin-8 could also control cell growth, tissue remodeling, and angiogenesis. mRNA for interleukin-8 and receptor CXCR1 rise in contracting skeletal muscle. Interleukin-8 generated by muscle cells could be localized and paracrinely directed at capillary endothelial cells, and attach to CXCR2 on the surface of capillary endothelial cells to induce new blood vessels within muscle.
Proposals to Inducing Interleukin-8 Expression
In normal physiology, interleukin-8 is low and hard to detect in cells. But it is sometimes induced to generate:
| Exclusion of proinflammatory cytokines |
Steroid hormones |
| Reactive oxygen species |
Bacteria |
| Viral products |
Drugs and Environment |
| Mutated tumor cells |
|
Related Diseases Interleukin 8
The cytokine IL-8 is a critical chemokine. It's also a major mediator of immune response (namely, magnetising and activating neutrophils and driving inflammatory responses). IL-8 is closely related to the activity of many diseases, especially in the following cases:
Inflammatory Diseases
IL-8 levels are high in many inflammatory conditions like rheumatoid arthritis, Crohn's disease and ulcerative colitis. It is usually in positive correlation with disease activity, that is, the worse the disease, the higher the IL-8 level.
Infection
There will be a huge rise in IL-8 level if bacterial infection, virus infection etc. It can release and cause immune cells to congregate at the site of infection, which can improve body's resistance to infection.
Malignant Tumors
In some tumors, IL-8 is believed to be related to tumor progression and metastasis. There are even reports that IL-8 in tumor patients is linked to disease progression and outcome.
Cardiovascular Disease
In cardiovascular conditions including atherosclerosis and heart disease, IL-8 is also thought to affect inflammatory responses and disease progression.
Idiopathic Pulmonary Fibrosis
Unknown-cause pulmonary fibrosis (IPF) is the most common undetermined-cause IIP. IPF is an autoimmune condition of interstitial pneumonia with chronic progressive fibrosis of unknown cause with lung-confined lesions, more frequent in the elderly, and pathologically and imagerically identical to UIP. There is no cure for IPF, but we do know that the lung interstitium will fibrosis after the disease has set in. The thick lung tissue becomes engorged and the ability of the lung tissue to transport oxygen has irreversibly been lost in massive fibrosis of the lung interstitial. It is a terminal illness of the airways.
Interleukin-8 and Idiopathic Pulmonary Fibrosis
A disorder in which lung fibrosis progresses and tends to be followed by lung inflammation is referred to as idiopathic pulmonary fibrosis. Since IL-8 is involved in lung inflammation, it will likely be a crucial player in the progression of IPF. IL-8 mostly brings neutrophils to the inflammation site, and activation can further injure lung tissue and exacerbate fibrosis. IL-8 could direct pulmonary fibrosis development by regulating the function and growth of fibroblasts. Fibroblasts are the primary cells responsible for the manufacture of collagen and other extracellular matrix materials, and their activity is directly related to the onset of IPF. IL-8 has also been detected in IPF patients, with high levels reported in the serum and bronchoalveolar lavage fluid, which could be a biomarker for the disease's diagnosis and progression. Since IL-8 is also implicated in the pathogenesis of IPF, IL-8-based or receptor-based therapeutics might offer IPF patients new treatment options.
Conclusion
It is all myofibroblasts that act in idiopathic pulmonary fibrosis (IPF). Maybe one of these is interleukin 8 (IL-8) and maybe this is what causes inflammation to be linked with fibrosis in idiopathic pulmonary fibrosis. It will take some more research to figure out what exactly IL-8 is doing to IPF and then the path to treat the disease will be repaved. Interleukin 8 is one of the major biomarkers for most chronic diseases, and it directly correlates with disease course and outcome. As long as you are vigilant about the IL-8, then you have something of a diagnostic, surveillance, and treatment manual for the disease. However what IL-8 does and what it does in other diseases is still unknown.
References
- Ziegenhagen, M., et al. Serum level of interleukin 8 is elevated in idiopathic pulmonary fibrosis and indicates disease activity. American journal of respiratory and critical care medicine. 1998, 157(3): 762-768.
- Zhu X., et al. The role of interleukin-8 in inflammatory response and its expression and regulation mechanism. Biomedicine. 2023, 13(2): 219-227.
- Cesta, M., et al. The role of interleukin-8 in lung inflammation and injury: implications for the management of COVID-19 and hyperinflammatory acute respiratory distress syndrome. Frontiers in pharmacology. 2022, 12: 808797.
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