Dear Dr. Mohammed

that SARS-CoV-1 can directly promote IL-6 secretion, this of course is not the only way it happens since IL-6 can be induced by so many types of cells and cytokines, Among all SARS-CoV-1 structural proteins (nucleocapsid N, spike S, envelop E and membrane M) only the nucleocapsid protein (N) significantly induced the activation of IL-6 promoter in human airway epithelial cell cultures. IL-6 gene expression is activated by the N protein which binds to the NF-kB regulatory element on IL-6 promoter and facilitates its translocation from cytosol to nucleus. The N protein is essential for IL-6 secretion to happen, since deletion of the C-terminus of the N protein resulted in the loss of function in the activation of IL-6.

It has been theorised that, in severe or critical COVID-19 patients, the pathogenic T cells and inflammatory monocytes may enter the pulmonary circulation and incite an inflammatory storm. IL‐6 is the cytokine that has been proven to be playing an important role in inflammatory reaction and immune response.[1] A similar conclusion was put forth by Xu et al[2], which implied a severe immune injury to the patient. IL-6 has previously proven to be an important indicator to assess the severity of infections and monitor prognosis.[3]

Thanks for your answer Dr. Haheel

It is a clear, but my quastion about a snp in the active site of protein structure of IL-6 and how it affects on cellular immune response.

IL-6 plays an important role on immune response by stimulation of antibody production and of effector T-cell development.

IL-6 is a cytokine featuring pleiotropic activity; it induces synthesis of acute phase proteins such as CRP, serum amyloid A, fibrinogen, and hepcidin in hepatocytes, whereas it inhibits production of albumin

Moreover, IL-6 can promote differentiation or proliferation of several nonimmune cells. Because of the pleiotropic activity, dysregulated continual production of IL-6 leads to the onset or development of various diseases.