Detection of Cytokines in Human Sural Nerve Biopsies: An Immunohistochemical and Molecular Study

in Acta Neuropathologica (2001), 101(4), 393-404

In vitro and in vivo models have implicated numerous cytokines as major modulators of inflammation, destruction and repair in the peripheral nervous system (PNS). The in situ production of cytokines in ... [more ▼]

In vitro and in vivo models have implicated numerous cytokines as major modulators of inflammation, destruction and repair in the peripheral nervous system (PNS). The in situ production of cytokines in human peripheral nerve disorders is still poorly documented. We studied the expression of interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-10, IL-4, IL-3 and nerve growth factor (NGF) in 35 human sural nerve biopsies using immunohistochemistry; additional reverse transcription-polymerase chain reaction and mRNA in situ hybridization were performed for IL-4 and NGF. Expression of IL-1 beta and TNF-alpha was shown in both morphologically normal nerves and various neuropathies, and macrophages appeared as their predominant source. Levels of IL-1 beta and TNF-alpha expression were significantly correlated (P < 0.01) with each other and with expression of NGF. Multiple endoneurial sources were suggested for IL-6 and IL-10 with low immunoreactivity in the vast majority of cases. Conversely, IL-4 and IL-3 expression were found in neuropathies of various etiologies and Schwann cells appeared to be a predominant source of IL-4 in double-labeling immunofluorescence studies. IL-3 immunoreactivity correlated with IL-1 beta, TNF-alpha and IL-6. In this retrospective study, no specific cytokine profile of expression could be assigned to a precise subgroup of neuropathies. This is the first report of IL-4 and IL-3 expression in human neuropathies, and it may be important given the potential role of these cytokines in modulating macrophage activity in the PNS. [less ▲]

Expression of several viral proteins during the varicella-zoster virus infectious cycle

Conference (1995)

Localization of varicella-zoster virus nucleic acids and proteins in human skin.

in Neurology (1995), 45(12 Suppl 8), 47-9

The pathogenic mechanisms involved in varicella-zoster virus (VZV) infections remain elusive. The pattern of cutaneous distribution of the IE63 protein and of the gpI (gE) and gpII glycoproteins with ... [more ▼]

The pathogenic mechanisms involved in varicella-zoster virus (VZV) infections remain elusive. The pattern of cutaneous distribution of the IE63 protein and of the gpI (gE) and gpII glycoproteins with their corresponding genome sequences during VZV infections was studied by immunohistochemistry and in situ hybridization. Skin biopsy specimens were obtained from immunocompetent and immunocompromised patients with varicella, herpes zoster, or atypical VZV lesions. The first evidence for VZV infection consisted of the presence of IE63 in keratinocytes. In the vesicles and pustules, the viral transcripts gpI, gpII, and IE63 and the corresponding nucleic acids for gpI and gpII were identified in keratinocytes, sebocytes, Langerhans cells, dermal dendrocytes, monocytes/macrophages, and endothelial cells. The gpI and gpII glycorpoteins were essentially located on the cellular membranes while IE63 expression was generally restricted to the nuclei. In three biopsies of early herpes zoster, viral proteins were disclosed in dermal nerves and in perineurial type I dendrocytes. This was never encountered in varicella. Vasculitic changes and endothelial cell involvement were more prominent in varicella than in herpes zoster. It is concluded that the secondary viremia in varicella that affects the dermal endothelial cells is followed by a cell-to-cell spread to keratinocytes. In herpes zoster, the viral progression through cutaneous nerves primarily extends to the pilosebaceous units with a secondary involvement of epidermal keratinocytes, followed by a further spread to dermal cells. [less ▲]

Viral glycoproteins in herpesviridae granulomas

in American Journal of Dermatopathology (1994), 16(6), 588-592

Granulomatous reactions after varicella zoster virus (VZV) and herpes simplex virus (HSV) infections are rare, and their pathogenesis remains unclear. We studied by immunohistochemistry and in situ ... [more ▼]

Granulomatous reactions after varicella zoster virus (VZV) and herpes simplex virus (HSV) infections are rare, and their pathogenesis remains unclear. We studied by immunohistochemistry and in situ hybridization early granulomatous reactions after VZV and HSV infections. In the five cases studied, the VZV glycoproteins gp I and gp II were present in cells abutted to altered vessels, but the corresponding genome sequences were disclosed in similar locations in only one of these cases. In an immunocompromised patient with diffuse HSV eruption, HSV I antigens were present in cells of the reticular dermis, while viral nucleic acids were not evident. Immunophenotyping of the granulomas showed strong Mac 387 and CD68 positive labelings of macrophages/monocytes, without any involvement of Factor XIIIa-positive cells. These findings suggest that the major viral envelope glycoproteins, rather than complete viral particles could trigger granuloma formation following HSV and VZV skin infections. [less ▲]

Causative role of VZV in two fatal disseminated infections

Conference (1994)

Immunohistochemical detection of immediate early and late phase proteins expressed during the varicella-zoster virus cycle

in British Journal of Dermatology. Supplement (1994), 131(44), 64

Comparative immunohistochemical study of herpes-simplex and varicella-zoster infections

in Virchows Archiv. A : Pathological Anatomy and Histopathology (1993), 422(2), 121-126

Herpes simplex (HSV) and varicella-zoster (VZV) skin infections share so many histological similarities that distinguishing between them may prove to be impossible. We developed and characterized a new ... [more ▼]

Herpes simplex (HSV) and varicella-zoster (VZV) skin infections share so many histological similarities that distinguishing between them may prove to be impossible. We developed and characterized a new monoclonal antibody, VL8, IgG kappa isotype, directed to the VZV envelope glycoprotein gpI. Immunohistochemistry with VL8 appeared highly sensitive and specific on formalin-fixed paraffin-embedded biopsies and a clear-cut distinction between HSV and VZV infections was possible. The pattern of VL8 immunolabelling in VZV infections was strikingly different from that found in HSV infections studied with polyclonal antibodies to HSV I and II. Double immunolabelling revealed the VL8 positivity of sebaceous cells, endothelial cells, Mac 387-and CD68-positive monocyte-macrophages, and factor XIIIa-positive perivascular, perineural and interstitial dendrocytes. Intracytoplasmic VL8 labelling of endothelial cells and perivascular dendrocytes was found at the site of leukocytoclastic vasculitis. [less ▲]

La régulation de l'expression des gènes du virus de la varicelle et du zona

in Annales de Médecine Vétérinaire (1992), 136(8), 627-635

Varicella-zoster virus (VZV) belongs to the alphaherpesvirus family and shares many important structural and functional similarities with other members of the family such as herpes simplex virus type 1 ... [more ▼]

Varicella-zoster virus (VZV) belongs to the alphaherpesvirus family and shares many important structural and functional similarities with other members of the family such as herpes simplex virus type 1 (HSV-1). VZV is responsible for two different clinical syndromes, varicella which is the result of the primary infection and zoster which is due to virus reactivation remaining latent in the peripheral nervous system. VZV DNA is 124,884 base pair long and encodes four regulatory proteins (IE4, IE61, IE62 and IE63). Using transient expression systems, we have shown that IE4, IE62 and IE63 can regulate the expression of an indicator gene driven by various VZV promoter regions, demonstrating that these proteins play important roles in the infectious cycle. [less ▲]

Two-dimensional study of varicella-zoster virus proteins

in Archives Internationales de Physiologie, de Biochimie et de Biophysique (1992), 100(2), 39