Targeting inflammatory citokines to prevent constriction in tuberculous pericarditis and beyond?

The pathogenetic mechanisms underlying the development and progression of pericarditis to complicated pericarditis with recurrences, cardiac tamponade, and constrictive pericarditis is poorly understood [1].

Uncontrolled inflammation may lead the progression to chronic evolution and inflammatory cytokines in pericardial fluid may drive the process.

Previous studies have shown elevation of cytokines in pericardial fluid [2], and may predict a complicated course with recurrences [3].

In this pilot study [4], Shenje J. and colleagues explored the effect of adjunctive prednisolone treatment on the concentration of inflammatory markers in pericardial tuberculosis. Tuberculous pericarditis is the most common cause of pericardial diseases in Africa and developing countries, thus representing one of the most important pericardial diseases in a worldwide perspective [5]. Constrictive pericarditis is not uncommon as sequelae of the disease and the risk of developing this complication is one of the highest reported [6].

The authors collected pericardial fluid, plasma and saliva samples from fourteen patients with pericardial tuberculosis at multiple time points (0, 8 and 24 h). In the main study [7] prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis and hospitalization.

A strongly compartmentalised immune response was found. Prednisolone significantly reduced IL-6 concentrations in plasma by 8 h of treatment, IL-1beta concentrations in saliva, as well as IL-8 concentrations in both pericardial fluid and saliva by 24 h. The pilot study highlights the importance of inflammatory cytokines to drive the progression of pericarditis and its complication and also suggests the possibility to monitor the early effect of therapy by their testing from plasma or saliva.

Targeting the treatment to specific cytokines is an emerging option for refractory recurrent pericarditis with corticosteroid dependence and colchicine resistance, where treatment with anakinra (an IL 1 antagonist) is successful to reach remission and allow corticosteroids withdrawal [8,9].