Introduction:
Every action in the human body, like the release of hormones, metabolism and release of energy, regulation of body temperature, and production and maintenance of immune cells, is taken care of by a very important system in the body. This is called the circadian rhythm. This circadian rhythm is a key regulator of the cycle of sleeping and waking up in the human body. Without such internal biological clocks, all the physiological processes will be disrupted, which can result in havoc for an individual.
Circadian rhythm is responsible for both physiological and pathological processes in the body. Thus, it influences several immune-mediated diseases, including rheumatic diseases.
What Is the Role of Circadian Rhythm in Immune Functions?
The circadian rhythm can carry out all bodily functions through a center located in the suprachiasmatic nucleus of the brain. This center reacts to changes in the external environment and causes various changes in the body. For example, when there is darkness at night, melatonin is secreted, and in the morning, exposure to light reduces the secretion of melatonin.
Similarly, the immune system in the human body is subjected to a circadian rhythm. As a result, various immune cells and signaling pathways in the immune system exhibit circadian fluctuations. The circadian rhythm influences the body's ability to release defense cells, fight against antigens, and produce cytokines.
The immune system and the hematopoietic or precursor blood cells are secreted from the bone marrow at night. Thus, the presence of mature white blood cells to fight against the disease is also at its peak during the night hours.
How Does Circadian Rhythm Influence Rheumatic Diseases?
The circadian rhythm highly influences common rheumatic diseases that affect the bones and joints in many ways.
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The internal biological clock influences the pattern of disease activity in rheumatic diseases. For example, in rheumatoid arthritis, there is stiffness in the small joints in the late nights and early mornings. This is because there is an increase in the levels of inflammatory mediators like cytokines (IL-6) and tumor necrosis factor during late nights and early mornings. Also, the ability to suppress such inflammation in the body is executed by an anti-inflammatory hormone called cortisol. Since cortisol levels are low at night, subsiding inflammation at night time becomes difficult. This clearly shows that the pattern of disease activity is highly related to the circadian rhythm.
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In rheumatic diseases, there is dysregulation or dysfunction of the body's immune system. This process is influenced by the circadian rhythm as well.
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People with any kind of rheumatic disease tend to sleep for less time. This poor sleep pattern can alter the circadian rhythm and increase the pain caused by the disease. The disease severity is markedly increased especially in rheumatic diseases like osteoarthritis and rheumatoid arthritis. Also, there are severe flare-up cases due to altered circadian rhythm. This shows that the body's circadian rhythm controls the progression of rheumatic disease.
How Is Circadian Rhythm Used to Treat Rheumatic Diseases?
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Chronotherapy: Human’s understanding of the circadian rhythm has led to the development of a treatment modality called chronotherapy. Chronotherapy aims to understand each individual's circadian rhythm or sleep-wake pattern and administer medications to control the disease and its progression effectively. The main objective of chronotherapy is to look for the pattern of an individual's immune system activity, drug metabolism, and hormone secretion and give medications that accurately work at the right time. This, in turn, optimizes the effectiveness of a treatment given for any rheumatic disease.
For rheumatic disease, chronotherapy is used to keep track of the right timings to give anti-inflammatory medications, disease-modifying drugs, and other interventions to coincide with peak disease activity periods exactly. Additionally, for rheumatic disease, changes in habits and lifestyle become paramount. This involves optimizing sleep patterns and exercise routines. These changes are also incorporated into chronotherapeutic strategies.
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Administration of Glucocorticoids: Glucocorticoids are used as a treatment modality to treat diseases like rheumatoid arthritis. It is an anti-inflammatory medication that reduces the inflammation of joints. It is administered into the body based on the circadian rhythm of the affected individual, considering the release of natural hormones in the body. They are administered in the morning to align with the body's naturally released endogenous cortisol, thus enhancing the anti-inflammatory action.
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Use of TNF Inhibitors: To subside the action of tumor necrosis factor (TNF), certain TNF inhibitors and biological agents are administered at a specific time for optimal effectiveness against rheumatic diseases. The circadian rhythm of the patients determines this specific time of administration.
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Incorporation of Sleep Hygiene Practices: Proper sleeping patterns should be understood for managing any rheumatic condition. The severity of a rheumatic disease increases progressively with poor or disrupted sleep patterns. Hence, establishing a hygienic sleep routine is essential. In patients with insomnia, non-pharmacological modalities of treatment like cognitive behavioral therapy are done. Pharmacological management is avoided in such individuals as these drugs may interact with the drugs given for rheumatic disorders.
To incorporate healthy sleeping patterns, regulating the sleep-wake cycle is necessary. This is done through light exposure therapy, where patients are subjected to natural light during the day, and exposure to artificial light is minimized at night. Through these methods, a proper sleep schedule can be established among the patients.
Research and studies focusing on the circadian rhythm should be done to bring about interventional therapies for rheumatic diseases. This can help patients manage their painful conditions to a greater extent.
Conclusion:
Overall, it is clear that circadian rhythm is certainly a major factor that influences the disease pattern and progression of rheumatic diseases. Understanding this relationship between the internal biological clock and the pathophysiology of rheumatic diseases is paramount as it helps curate the right treatment plan for a particular affected individual. It also creates new avenues for innovative treatment approaches based on the diurnal variations. Doctors and rheumatologists should also consider the changes brought about by the circadian rhythm for effective management of a rheumatic disorder.
