CYTOKINE PRODUCTION IN THE NERVOUS-SYSTEM OF MICE DURING ACUTE AND LATENT INFECTION WITH HERPES-SIMPLEX VIRUS TYPE-1

Immunocytochemistry on serial paraffin sections was used to monitor th e production dynamics of cytokines (IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha) and viral antigens in the trigeminal ganglion (TG) and the central side of the dorsal root entry zone (DRE) of mice, followi ng infection of the cornea with herpes simplex virus type 1. In normal TG, scattered satellite cells were TNF-alpha(+) and in the DRE, TNF-a lpha(+) and/or low numbers of IL-6(+) cells were detected. On day 3 af ter infection, foci of TG neurons with viral antigens were surrounded by large numbers of TNF-alpha(+) and/or IL-6(+) cells and low numbers of IFN-gamma(+) cells. IL-2(+) and/or IL-4(+) cells appeared later, wh en viral antigens had almost cleared. In the TG, the most striking cha nges occurred with TNF-alpha, with respect to its source (satellite ce lls, Schwann cells and infiltrating cells) and the extent and long dur ation of its production. TNF-alpha was the predominant cytokine throug hout acute and latent infection and even by day 30, numbers of satelli te cells expressing this cytokine were three times higher than those i n normal ganglia. Moreover, in the DRE, TNF-alpha was the only cytokin e detected during virus clearance and again, its production continued, along with that of IL-6, on days 20 to 30, in both infiltrating cells and astrocytes. Thus, cytokines, particularly TNF-alpha and perhaps I L-6, from infiltrating cells and resident glial cells may have a role both in virus clearance and in normal homeostatic mechanisms in the ne rvous system such as repair and protection of neurons from damage.