The role of the innate immune response in detecting RNA viruses is crucial for the establishment of proper inflammatory and antiviral responses. Different receptors, known as pattern recognition receptors (PRRs), are present in the cytoplasm, endosomes, and on the cellular surface. These receptors have the capacity to sense the presence of viral nucleic acids as pathogen-associated molecular patterns (PAMPs). This recognition leads to the induction of type 1 interferons (IFNs) as well as inflammatory cytokines and chemokines. In this review, we provide an overview of the significant involvement of cellular RNA helicases and Toll-like receptors (TLRs) 3, 7, and 8 in antiviral immune defenses.
Background
Interleukin‐6 (IL‐6) is produced by and impacts different cell types in human. IL‐6 is associated with different diseases and viral infections, including COVID‐19. To our knowledge, no normal values were reported for IL‐6 in the blood of healthy individuals. We have reviewed and performed a meta‐analysis on a total of 140 studies, including 12,421 values for IL‐6 in the blood of healthy adult donors. Among these studies, 83 did not report a mean value and the standard deviation. Therefore, for the statistical analysis, we used the values reported in 57 studies, which included 3166 values for IL‐6.
Results
The reported values for IL‐6 in the blood of healthy donors varied between 0 and 43.5 pg/ml. The pooled estimate of IL‐6 was 5.186 pg/ml (95% confidence interval [CI]: 4.631, 5.740). As the age increased by 1 year, IL‐6 values increased by 0.05 pg/ml (95% CI: 0.02, 0.09; p < .01). Though the heterogenicity, as determined by I2 statistics, was high in our study, the differences in IL‐6 values are still at the level of a few pg/ml, which might be related to the differences in the conditions that influence IL‐6 production in the healthy population.
Conclusions
This is the first meta‐analysis reporting the levels of IL‐6 in the blood of healthy donors based on a large number of studies and donors. Therefore the 95% CI values determined in our study could well serve as a reference range for quick decision‐making in clinical interventions, particularly those aiming to inhibit IL‐6, especially urgent interventions, for example, COVID‐19.
For long, the immune system has been thought of as an effector mechanism reacting to antigenic challenge with defensive responses designed to eliminate 'foreign' material and return to a standby or surveillance mode. However, the recent concept now supported by substantial evidence suggests that immunity is not effector biased but is also a sensory organ and forms part of an integrated homeostatic network. The bidirectional information flow between the neuroendocrine and immune systems functions to maintain and protect the internal homeostasis of the organism. The paradox of this interwined function is that homeostasis may require the neuroendocrine system to work for or against the immune system, as is the case in infection. Potential dangers necessitate activation of the immune system, and such a response may pose risks to the integrity of the host. This occurs when an overly vigorous response may be detrimental and kill the host, as is the case of toxic shock syndrome. Therefore, the constant monitoring role of the neuroendocrine system to control and, when necessary, regulate the function of the immune system is crucial for the homeostatic integrity of the host. This reciprocity of functional need determines the mode of action to determine the context of a perceived threat and the best way to respond. Any breakdown in this two-way communication may manifest itself in problems such as autoimmunity, septic shock, or chronic infection. In this article, we review our current knowledge of circadian rhythm and its relation to the immune response.
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