The Role of gp130 Cytokines in Tuberculosis

Abstract

Protective immune responses to Mycobacterium tuberculosis (Mtb) infection substantially depend on a delicate balance within cytokine networks. Thus, immunosuppressive therapy by cytokine blockers, as successfully used in the management of various chronic inflammatory diseases, is often connected with an increased risk for tuberculosis (TB) reactivation. Hence, identification of alternative therapeutics which allow the treatment of inflammatory diseases without compromising anti-mycobacterial immunity remains an important issue. On the other hand, in the context of novel therapeutic approaches for the management of TB, host-directed adjunct therapies, which combine administration of antibiotics with immunomodulatory drugs, play an increasingly important role, particularly to reduce the duration of treatment. In both respects, cytokines/cytokine receptors related to the common receptor subunit gp130 may serve as promising target candidates. Within the gp130 cytokine family, interleukin (IL)-6, IL-11 and IL-27 are most explored in the context of TB. This review summarizes the differential roles of these cytokines in protection and immunopathology during Mtb infection and discusses potential therapeutic implementations with respect to the aforementioned approaches.

Risk of Reactivation of Hepatitis B Virus (HBV) and Tuberculosis (TB) and Complications of Hepatitis C Virus (HCV) Following Tocilizumab Therapy: A Systematic Review to Inform Risk Assessment in the COVID-19 Era

“…IL-6 also influences the mileu of other cytokines, including IL-12, IL-23, and type 1 interferons (IFNs), thus playing a role in a complex interaction of factors responsible for co-ordinating macrophage, neutrophil and T-cell activation, with the potential to mediate both pro-inflammatory and anti-inflammatory effects ( 58 , 59 ) ( Figure 2 ). These roles may have varied influence, depending on the dose and route of inoculum, in different animal hosts, and in acute vs. chronic infection ( 60 ). Overall, the effect of IL-6 blockade on outcomes of mycobacterial infection may be modest, and less than that associated with TNF-blockade ( 61 ).…”

Pleiotropic Effect of IL-6 Produced by B-Lymphocytes During Early Phases of Adaptive Immune Responses Against TB Infection

“…In particular, specific activities of IL-6 produced by B-cells remain obscure despite its abundance in TB-infected lungs (8,9). IL-6 is a pleiotropic gp130 cytokine that is involved in several immune reactions and displays pro-and anti-inflammatory activity depending upon its cellular sources and the phase of the inflammatory process (14). IL-6 is produced by a variety of cells, including T-and B-cells, macrophages, and CD11c + cells.…”

The Effect of Natural-Based Formulation (NBF) on the Response of RAW264.7 Macrophages to LPS as an In Vitro Model of Inflammation

“…Macrophages play an important role in the host-immune interaction during infection [ 1 ]. Their activation may lead to various acute and chronic inflammatory diseases such as rheumatoid arthritis, tuberculosis, asthma, sinusitis, Crohn’s disease, ulcerative colitis, hepatitis, and viral infections [ 2 , 3 , 4 ]. Macrophages can be activated by different stimuli, including lipopolysaccharide (LPS, an endotoxin from Gram-negative bacteria), leading to the release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6 [ 5 ], inflammatory mediators such as nitric oxide (NO), prostaglandin (PG) E2, and the production of reactive oxygen species (ROS), which significantly contribute to the induction of peripheral and neuro-inflammatory diseases [ 6 , 7 ].…”