Increased susceptibility to pneumonia due to tumour necrosis factor inhibition and prospective immune system rescue via immunotherapy

Abstract

Immunomodulators such as tumour necrosis factor (TNF) inhibitors are used to treat autoimmune conditions by reducing the magnitude of the innate immune response. Dampened innate responses pose an increased risk of new infections by opportunistic pathogens and reactivation of pre-existing latent infections. The alteration in immune response predisposes to increased severity of infections. TNF inhibitors are used to treat autoimmune conditions such as rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, transplant recipients, and inflammatory bowel disease. The efficacies of immunomodulators are shown to be varied, even among those that target the same pathways. Monoclonal antibody-based TNF inhibitors have been shown to induce stronger immunosuppression when compared to their receptor-based counterparts. The variability in activity also translates to differences in risk for infection, moreover, parallel, or sequential use of immunosuppressive drugs and corticosteroids makes it difficult to accurately attribute the risk of infection to a single immunomodulatory drug. Among recipients of TNF inhibitors, Mycobacterium tuberculosis has been shown to be responsible for 12.5-59% of all infections; Pneumocystis jirovecii has been responsible for 20% of all non-viral infections; and Legionella pneumophila infections occur at 13-21 times the rate of the general population. This review will outline the mechanism of immune modulation caused by TNF inhibitors and how they predispose to infection with a focus on Mycobacterium tuberculosis, Legionella pneumophila, and Pneumocystis jirovecii. This review will then explore and evaluate how other immunomodulators and host-directed treatments influence these infections and the severity of the resulting infection to mitigate or treat TNF inhibitor-associated infections alongside antibiotics.

The Role of Chlamydia pneumoniae in the Aetiology of Autoimmune Diseases

“…Pharmacotherapy of autoimmune disorders with corticosteroids and disease-modifying antirheumatic drugs (DMARDs) such as tumour necrosis factor (TNF) inhibitors can increase the susceptibility to bacterial infection, including bacterial pneumonia [ 14 - 16 ]. It might, therefore, be argued that such medication could be a confounding variable that accounts for our finding.…”

Relationship between serum TNF-α, IL-6, and IL- 10 levels and disease severity, and changes in the cytokines after treatment in patients with bacterial community-acquired pneumonia

“…TNF is secreted mainly by activating macrophages, monocytes, and T lymphocytes, causing damage to neighboring cells by direct contact 31 . There are two types of TNF molecules, TNF-α and TNF-β, which play a vital role in the immune mechanism against bacterial and fungal invasion, significantly increased in pneumonia caused by S. pneumoniae, K. pneumoniae, P. aeruginosa, L. pneumophila, Cryptococcus neoformans, Aspergillus fumigatus, and Pneumocystis carinii 13,32,33 . Thus, changes in serum cytokine tend to be increased in bacterial pneumonia and relate to the microbiology etiology, due to endotoxins of bacteria.…”

The relationship between neighborhood economic deprivation and community-acquired pneumonia related admissions in Maryland

“…These cytokines contribute to characteristic pneumonia symptoms, like fever, cough, and chest pain. TNF-α, especially, has been identified as an important cytokine, responsible for regulating several cellular activities that lead to pneumonia’s clinical manifestations ( 17 – 19 ). It promotes the recruitment of neutrophils, increased vascular permeability, and consolidation of lung tissues.…”

“…It promotes the recruitment of neutrophils, increased vascular permeability, and consolidation of lung tissues. Targeting the inflammatory cascade provides a potential therapeutic approach, given its significant role in the exacerbation of pneumonia symptoms ( 19 ).…”