The role of T_H1 and T_H2 cytokines in HSV-1-induced corneal scarring

Purpose: To determine the relative impact of T_H1 and T_H2 cytokines on the induction of corneal scarring. Methods: BALB/c and C₅₇BL/6 mice were infected ocularly with herpes simplex virus type 1 (HSV-1)-recombinant viruses expressing either IL-2, IL-4, IFN-γ, IL-12p35, or IL-12p40. Parental virus and recombinant viruses in one group (dLAT2903, HSV-IL-2, HSV-IL-4, and HSV-IFN-γ) contained an intact neurovirulence gene, γ34.5, while the second set of recombinant viruses (DM33, dbl-IL2, dbl-IL4, dbl-IFNγ, dbl-IL12p35, and dbl-IL12p40) lacked the γ34.5 gene. Results: In the presence of γ34.5, viruses that expressed either IL-2 or IL-4 reduced the severity of corneal scarring in both BALB/c and C57BL/6 mice compared with the parental virus. In contrast, the recombinant virus expressing IFN-γ was not protective in BALB/c mice, while it exacerbated corneal scarring in C₅₇BL/6 mice compared with the parental or wt McKrae virus. In the absence of the γ34.5 gene, recombinant viruses expressing IL-2, IL-4, IFN-γ, IL-12p35, or IL-12p40 did not induce any corneal scarring. Conclusions: Our results suggest the following: (1) IL-2 and IL-4 are both involved in protection against HSV-1-induced corneal scarring; (2) IFN-γ is not involved in protection against HSV-1-induced corneal scarring; and (3) the degree of neurovirulence plays a major role in the protection against or induction of corneal scarring.