The Impact of Targeted Therapy on Microorganism in Patients With Psoriasis

Introduction As numerous studies have identified TNF-α, TH-17 and IL-17 as particularly major roles governing the inflammatory cascade in psoriasis, target therapies, including TNF-α and TH-17 antagonists, have represented major breakthrough in the treatment of psoriasis. It is well known that TNF-α plays an important role in the immune response to viral infections, which is attributed to direct inhibition of viral replication, killing of virally infected cells, induction of FasL-dependent CD8+ T-lymphocyte effector pathways through TNF/TNF receptor 2 interaction and promote inflammatory response indirectly.Additionally, it has been shown that treatment with TNF-α antagonists is associated increased viral replication in virus-inoculated rats, progressive loss of CD4+ and CD8+ T cells and decreased level of TNF-α and interferon. A transient decreased T cell responsiveness was also observed in some patients treated with TNF-α antagonists.10 TNF-α can inhibit CMV production in certain cell types and the CMV major immediate early promoter is inhibited by TNF-α. Increased TNF production has been reported during CMV infection, which also displays anti-CMV activity in vitro.

TNF-α is also involved in direct control of HPV infection by induction of apoptosis of HPV-infected cells, arresting growth of HPV-infected keratinocytes and down-regulation of HPV-gene transcription, stimulation of inflammatory response and up-regulation of HLA class I components in antigen-presenting cells. E6 protein of HPV-16 is known to directly bind to TNF receptor 1 and abrogate TNF-induced apoptosis of the host cells. Recent studies have shown a high prevalence of HPV DNA in psoriatic skin and increased HPV5 antibodies in patients with psoriasis. It seems that psoriatic skin may be specifically permissive for HPV. Increased pap smear abnormalities has been observed in patients with inflammatory bowel diseases receiving TNF-α antagonists. However, the specific effects of anti-TNF therapy on HPV carriage and HPV-associated disease remain unknown.

Epstein-Barr virus (EBV) is associated with several B-cell and epithelial-cell malignancies, especially in patients under the immunosuppressive treatment. Increased risk of lymphoproliferative disorders in patients treated with TNF-α antagonists has been addressed. Case reports of EBV-associated lymphoproliferative diseases that regressed after withdrawal of anti-TNF-α drugs had been also described. Thus, the concern of the increased risk at least in part caused by immunosuppression of anti-TNF therapy, which may cause a consecutive EBV reactivation, emerged but was not proven yet.

Anti-TNF-α drugs, including monoclonal antibody against TNF-α (infliximab and adalimumab) and soluble TNF receptor (etanercept), are recognized as a risk factor for opportunistic infections. A recent study demonstrated a higher risk of opportunistic infections for patients receiving adalimumab than etanercept, with a 10- to 17-fold differences in risk. However, most knowledge of latent viral reactivation during anti-TNF treatment has come from studies of patients with inflammatory bowel disease and rheumatoid arthritis. Moreover, these studies mainly focus on herpesviruses and viral hepatitis. Several case reports in which EBV, CMV,and HPV infection complicated therapy with TNF-α antagonists in patients with psoriasis have also been reported.

IL-17 is a proinflammatory cytokine that is produced by a variety of cells, including a newly identified subset of activated CD4+ T cells (Th17 cells), γδT cells, CD8+ cells and NKT cells. There is evidence to support a protective role for IL-17 in the host defense against extracellular bacterial infections, including Klebsiella pneumonia,38 Bacteroides fragilis and Escherichia coli. A recent study also showed IL-17 is essential for human immunity against common fungus Candida albicans.