The role of interleukin (IL)-6 in health and disease has been under a lot of scrutiny in recent years, particularly during the recent COVID-19 pandemic. The inflammatory pathways in which IL-6 is involved are also partly responsible of the development and progression of rheumatoid arthritis (RA), opening interesting perspectives in terms of therapy. Anti-IL-6 drugs are being used with variable degrees of success in other diseases and are being tested in RA. Results have been encouraging, particularly when anti-IL-6 has been used with other drugs, such as metothrexate (MTX). In this review we discuss the main immunologic aspects that make anti-IL-6 a good candidate in RA, but despite the main therapeutic options available to target IL-6, no gold standard treatment has been established so far.

Lipopolysaccharides (LPSs) are bacterial surface glycolipids, produced by Gram-negative bacteria. LPS is known to determine acute inflammatory reactions, particularly in the context of sepsis. However, LPS can also trigger chronic inflammation. In this case, the source of LPS is not an external infection, but rather an increase in endogenous production, which is usually sustained by gut microbiota (GM), and LPS contained in food. The first site in which LPS can exert its inflammatory action is the gut: both GM and gut-associated lymphoid tissue (GALT) are influenced by LPS and shift towards an inflammatory pattern. The changes in GM and GALT induced by LPS are quite similar to the ones seen in IBD: GM loses diversity, while GALT T regulatory (Tregs) lymphocytes are reduced in number, with an increase in Th17 and Th1 lymphocytes. Additionally, the innate immune system is triggered, through the activation of toll-like receptor (TLR)-4, while the epithelium is directly damaged, further triggering inflammation. In this review, we will discuss the importance of the crosstalk between LPS, GM, and GALT, and discuss the possible implications.

Patients with COVID-19 show a high prevalence of liver injury. The pattern of this liver damage is still not fully understood. Different etiopathogenetic factors may concur; from a direct cytopathic effect, once the virus binds to the ACE-2 receptors, to the immune-mediated collateral damage, due to cytokine storm. The presence of pre-existing chronic liver disease is a contributing factor for acute organ damage during SARS-CoV2 infection. Last but not least, treatments probably play a role, also, in determining hepatotoxicity: many of the drugs we have used or are still using to treat COVID-19, combined with non-invasive ventilation, are known to sometimes determine acute liver injury. Although liver damage associated with COVID-19 is often transient and can resolve without any special treatment, it is important to understand the underlying mechanisms, particularly to better treat its more severe forms.