Spontaneous or interferon-γ-induced T-cell infiltration, HLA-DR and ICAM-1 expression in genitoanal warts are associated with TH1 or mixed TH1/TH2 cytokine mRNA expression profiles

Abstract

The purpose of the study was to investigate the cytokine gene expression patterns and immunohistochemical characteristics of genitoanal warts in order to obtain a clue as to the immunological mechanisms possibly relevant for wart regression or persistence. We analysed surgically removed warts from 11 patients, 2 of whom were immunosuppressed. Lesions of five of the nine otherwise healthy individuals were additionally treated with intralesional interferon-gamma (IFN gamma) prior to surgery. Invasion of CD4+ T cells into the papillomas and HLA-DR and ICAM-1 expression on keratinocytes were found in two otherwise healthy patients and were intensified by intralesional IFN gamma in four of five patients. The mRNA expression patterns in seven of eight non-recurrent warts were compatible with a predominant TH1 or mixed TH1/TH2 cytokine profile. In contrast, in recalcitrant warts of three patients (one healthy, two immunocompromised) histological signs of immunore-activity and TH1-like cytokine mRNA expression were not detected. In recurrent warts of a renal transplant patient, IL-4 and IL-5 mRNA expression was repeatedly found suggesting a predominant TH2 response. In conclusion, immunoreactivity to genitoanal warts such as T-cell infiltration, HLA-DR and ICAM-1 expression was associated with a predominant TH1 or mixed TH1/ TH2 cytokine mRNA expression profile.

Intralesional immunotherapy with killed Mycobacterium indicus pranii vaccine for the treatment of extensive cutaneous warts

“…Keratinocytes are both the main source of the inflammatory cytokines as well as the main target of HPVs. [11,23] Thus by manipulating the local immunological milieu, it may be possible to achieve a therapeutic response against both clinical and latent cutaneous HPV infections. Resistant multiple cutaneous warts are a therapeutic challenge.…”

Expression of Toll-Like Receptors in Verruca and Molluscum Contagiosum

“…The precise mechanism of the human immune response to these viral skin diseases remains unclear. Cutaneous viral infections have been proposed to induce localized inflammatory and antiviral responses that are believed to result in the resolution of viral skin lesions (25, 26). Keratinocytes are one of the first cutaneous cell types to encounter various microbes including the papilloma and molluscum viruses.…”

Genetic susceptibility to HPV infection and cervical cancer

“…While Th1 cytokines stimulate the cellular immune response, Th2 cytokines repress it. A Th1 response was correlated with wart regression (63), and less severe HPV-associated disease (64,65). Low levels of intratumoral IFN-g were related to a poor prognosis for SCCC (66).…”